bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Sim1 gene dosage on the development of the paraventricular and supraoptic nuclei of the hypothalamus
Authors: Duplan Sabine Michaëlle , Boucher Francine , Alexandrov Lubomir , Michaud Jacques L. 
Published: December 2009

AbstractThe bHLH‐PAS transcription SIM1 is required for the development of all neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Mice with a loss of Sim1 die within a few days of birth, presumably because of the lack of a PVN and SON. In contrast, mice with a decrease of Sim1 survive, are hyperphagic and become obese. The mechanism by which Sim1 controls food intake remains unclear. Here we show that the development of specific PVN and SON cell types is sensitive to Sim1 gene dosage. Sim1 haploinsufficiency reduces the number of vasopressin (AVP)‐ and oxytocin‐producing cells in the PVN by about 50 and 80%, respectively, but does not affect the development of Crh, Trh and Ss neurons. A decrease of AVP‐producing cells increases the sensitivity of Sim1 heterozygous mice to chronic dehydration. Moreover, retrograde labelling showed a 70% reduction of PVN neurons projecting to the dorsal vagal complex, raising the possibility that a decrease of these axons contributes to the hyperphagia of Sim1+/− mice. Sim1 haploinsufficiency is thus associated with a decrease of several PVN/SON cell types, which has the potential of affecting distinct homeostatic processes.
Dermoscopic features of Bowen’s disease in Asians
Authors: Mun J‐H , Kim S‐H , Jung D‐S , Ko H‐C , Kwon K‐S , Kim M‐B 
Published: December 2009

AbstractBackground  Previously, dermoscopic features of Bowen’s disease (BD) were extensively investigated in two studies, but there were some discrepancies. The dispute necessitated a further study concerning the dermoscopic features of BD.Objective  To describe the dermoscopic features of BD in Asians and to assess dermoscopy as a post‐treatment monitoring tool of BD.Materials and methods  Dermoscopic examinations of histopathologically diagnosed 26 BD lesions were performed to evaluate for the presence of various dermoscopic features. In addition, the correlating changes of dermoscopic features and histopathological results before and after treatments were assessed in five patients with BD.Results  Dermoscopically, 10 lesions were pigmented and 16 lesions were non‐pigmented. The most frequent dermoscopic findings of BD were vascular structures (96%) and a scaly surface (96%). Among vascular structure, glomerular vessels were most frequently observed (77%). The other vascular structures in our study were linear irregular vessels, dotted vessels, polymorphous/atypical vessels and arborizing vessels. Among five patients who had been treated with either photodynamic therapy or 5% imiquimod cream, four patients revealed disappearance of dermoscopic vascular structures, but one patient showed remaining vascular structures after treatment. Skin biopsy from treated lesions disclosed clearance of BD in four patients who had no vascular structures but remaining BD in the patient whose dermoscopic finding displayed no disappearance of vascular structures.Conclusions  Vascular structures, especially glomerular vessels plus a scaly surface, were common dermoscopic findings of BD in Asians. In addition, existence of dermoscopic vascular structures after treatment appears to be associated with residual disease.
Authors’ willingness for second‐opinion teledermatology in difficult‐to‐manage cases: ‘an online survey’
Authors: Kanthraj GR 
Published: December 2009

AbstractBackground  Expert non‐availability for an instant difficult‐to‐manage case may limit the online discussion group to provide second‐opinion teledermatology for registered dermatologists. Author‐based second‐opinion teledermatology (AST) is proposed and assessment of authors’ response to answer queries and their willingness to participate in teledermatology consultation is analysed.Materials and methods  Authors of 292 articles from seven non‐open access dermatology and three general medical journals addressing difficult‐to‐manage cases from June 2007 to December 2008 participated in this online dermatology authors’ survey. Authors’ response to reprint requests, answer literature queries and willingness to offer second‐opinion teledermatology were the main outcome measures. Perceived views were also documented.Results  The scores for reprints requests vs. received were (χ2 = 13.57, n = 292), P = 0.000. The scores for articles read, analysed and literature queries sent vs. authors answered were (χ2 = 11.09, n = 190), P = 0.001. The scores for authors responded to reprints vs. willing to offer second‐opinion teledermatology consultation were (χ2 = 5.65, n = 190), P = 0.017 and authors responded to reprint requests, answered queries and willing to offer second‐opinion (χ2 = 5.65, n = 190), P = 0.017.Conclusion  A dermatologist obtains literature, answered queries and constructive suggestions with additional informative material and pools second‐opinions from the authors using their e‐mail to deliver quality health care. AST is an alternative to online discussion group for second‐opinion teledermatology practice in difficult‐to‐manage cases. Uniform international laws are to be framed to facilitate telemedicine care for a difficult‐to‐manage case.
Psoriasis is independently associated with psychiatric morbidity and adverse cardiovascular risk factors, but not with cardiovascular events in a population‐based sample
Authors: Schmitt J , Ford DE 
Published: December 2009

AbstractBackground  Psoriasis may significantly reduce quality of life. Previous studies reported an association of psoriasis and cardiovascular risk factors and cardiovascular events. The extent to which psoriasis is associated with psychiatric morbidity and the role of psychiatric comorbidity as a potential confounder of the association between psoriasis and cardiovascular morbidity require further investigation.Objectives  To study the association between psoriasis, psychiatric morbidity and cardiovascular morbidity.Methods  Case–control study utilizing an interdisciplinary administrative outpatient database from Germany. Patients with confirmed diagnosis of prevalent psoriasis within the study period (2003–2004) (n = 3147, mean age 57 years) were individually matched for age and gender with 3147 controls without psoriasis. The relationship of psoriasis with psychiatric morbidities (depression, stress‐related disorders, behaviour disorders and schizophrenic disorders), cardiovascular risk factors (diabetes, hypertension, obesity and dyslipidaemia) and cardiovascular events [myocardial infarction (MI), stroke] was investigated using logistic and linear regression models.Results  Crude analyses suggested an association of psoriasis with depression, stress‐related disorders, behaviour disorders and cardiovascular risk factors, but not with MI [odds ratio (OR) 1.14; 95% confidence interval (95% CI) 0.81–1.62] or stroke (OR 0.97; 95% CI 0.61–1.54). Multivariate models controlling for age, gender and consulting behaviour indicated that psoriasis is independently associated with depression (OR 1.49; 95% CI 1.20–1.86), stress‐related disorders (OR 1.41; 95% CI 1.22–1.62), behaviour disorders (OR 1.58; 95% CI 1.05–2.39), diabetes (OR 1.21 95% CI 1.04–1.40), hypertension (OR 1.34; 95% CI 1.18–1.51), dyslipidaemia (OR 1.29; 95% CI 1.07–1.55), and obesity (OR 1.63; 95% CI 1.39–1.90). For each psychiatric condition, the likelihood of being affected significantly increased with each physician visit due to psoriasis, suggesting that the risk of psychiatric comorbidity increases with the severity of psoriasis.Conclusion  Psoriasis appears to be independently associated with major psychiatric disorders and with cardiovascular risk factors, but not with cardiovascular events.
Linking biotic homogenization to habitat type, invasiveness and growth form of naturalized alien plants in North America
Authors: Qian Hong , Guo Qinfeng 
Published: December 2009

AbstractAim  Biotic homogenization is a growing phenomenon and has recently attracted much attention. Here, we analyse a large dataset of native and alien plants in North America to examine whether biotic homogenization is related to several ecological and biological attributes.Location  North America (north of Mexico).Methods  We assembled species lists of native and alien vascular plants for each of the 64 state‐ and province‐level geographical units in North America. Each alien species was characterized with respect to habitat (wetland versus upland), invasiveness (invasive versus non‐invasive), life cycle (annual/biennial versus perennial) and habit (herbaceous versus woody). We calculated a Jaccard similarity index separately for native, for alien, and for native and alien species. We used the average of Jaccard dissimilarity index (1 − Jaccard index) of all paired localities as a measure of the mean beta diversity of alien species for each set of localities examined in an analysis. We used a homogenization index to quantify the effect of homogenization or differentiation.Results  We found that (1) wetland, invasive, annual/biennial and herbaceous alien plants markedly homogenized the state‐level floras whereas non‐invasive and woody alien plants tended to differentiate the floras; (2) beta diversity was significantly lower for wetland, invasive, annual/biennial and herbaceous alien plants than their counterparts (i.e. upland, non‐invasive, perennial and woody alien plants, respectively); and (3) upland and perennial alien plants each played an equal role in homogenizing and differentiating the state‐level floras.Main conclusions  Our study shows that biotic homogenization is clearly related to habitat type (e.g. wetland versus uplands), species invasiveness and life‐history traits such as life cycle (e.g. annual/biennial and herbaceous versus woody species) at the spatial scale examined. These observations help to understand the process of biotic homogenization resulting from alien vascular plants in North America.
Comparison of direct and indirect methods of intra‐abdominal pressure measurement in normal horses
Authors: Munsterman Amelia S. , Hanson R. Reid 
Published: December 2009

AbstractObjectives –To develop a direct method for measuring intra‐abdominal pressures in the standing horse, identify a reference interval for direct intra‐abdominal pressures, compare these pressures to indirect intra‐abdominal pressures measured from the bladder, and determine the optimal bladder infusion volume for indirect pressure measurement.Design –Prospective, experimental study.Setting –A university‐based equine research facility.Animals –Ten healthy adult horses, 5 males and 5 females.Interventions –Direct intra‐abdominal pressures were measured through an intraperitoneal cannula and zeroed at the height midway between the height of the tuber ishii and point of the shoulder. Indirect measurements of intra‐abdominal pressure were performed by measuring intravesicular pressures through a transurethral catheter zeroed at the tuber ishii.Measurements and Main Results –Direct pressure measurements obtained in the standing horse were subatmospheric (mean, −1.80 cm H2O; SD, 1.61 cm H2O; 95% CI, −2.80 to −0.80) and were shown to decrease as the horse's weight increased (Pearson'sr=−0.67,P=0.04), with no effect of head position (P=0.15). Mean baseline indirect pressure measurements (mean, −8.63 cm H2O; SD, 4.37 cm H2O; 95% CI, −13.05 to −4.21) were significantly different from the pressures measured directly from the abdomen (P<0.001). Indirect pressure measurements were noted to increase with increasing volumes infused into the bladder, and were statistically different at a volume of 100 mL (P=0.004). There was low to moderate correlation between direct and indirect pressure measurements of intra‐abdominal pressure over a range of fluid volumes infused into the bladder (Pearson's correlation range −0.38 to 0.58).Conclusion –Pressures measured directly in the standing horse were subatmospheric, and increased as the horse's weight increased. Indirect pressures measured were altered by increasing volumes infused in the bladder. There was no significant correlation between the 2 methods of intra‐abdominal pressure measurement.
Bimolecular fluorescence complementation: lighting up seven transmembrane domain receptor signalling networks
Authors: Rose Rachel H , Briddon Stephen J , Holliday Nicholas D 
Published: December 2009

There is increasing complexity in the organization of seven transmembrane domain (7TM) receptor signalling pathways, and in the ability of their ligands to modulate and direct this signalling. Underlying these events is a network of protein interactions between the 7TM receptors themselves and associated effectors, such as G proteins and β‐arrestins. Bimolecular fluorescence complementation, or BiFC, is a technique capable of detecting these protein–protein events essential for 7TM receptor function. Fluorescent proteins, such as those from Aequorea victoria, are split into two non‐fluorescent halves, which then tag the proteins under study. On association, these fragments refold and regenerate a mature fluorescent protein, producing a BiFC signal indicative of complex formation. Here, we review the experimental criteria for successful application of BiFC, considered in the context of 7TM receptor signalling events such as receptor dimerization, G protein and β‐arrestin signalling. The advantages and limitations of BiFC imaging are compared with alternative resonance energy transfer techniques. We show that the essential simplicity of the fluorescent BiFC measurement allows high‐content and advanced imaging applications, and that it can probe more complex multi‐protein interactions alone or in combination with resonance energy transfer. These capabilities suggest that BiFC techniques will become ever more useful in the analysis of ligand and 7TM receptor pharmacology at the molecular level of protein–protein interactions.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00685.x
Dopamine transporter down‐regulation following repeated cocaine: implications for 3,4‐methylenedioxymethamphetamine‐induced acute effects and long‐term neurotoxicity in mice
Authors: Peraile I , Torres E , Mayado A , Izco M , Lopez‐Jimenez A , Lopez‐Moreno JA , Colado MI , O'Shea E 
Published: December 2009

Background and purpose: 3,4‐Methylenedioxymethamphetamine (MDMA) and cocaine are two widely abused psychostimulant drugs targeting the dopamine transporter (DAT). DAT availability regulates dopamine neurotransmission and uptake of MDMA‐derived neurotoxic metabolites. We aimed to determine the effect of cocaine pre‐exposure on the acute and long‐term effects of MDMA in mice.Experimental approach: Mice received a course of cocaine (20 mg·kg−1, ×2 for 3 days) followed by MDMA (20 mg·kg−1, ×2, 3 h apart). Locomotor activity, extracellular dopamine levels and dopaminergic neurotoxicity were determined. Furthermore, following the course of cocaine, DAT density in striatal plasma membrane and endosome fractions was measured.Key results: Four days after the course of cocaine, challenge with MDMA attenuated the MDMA‐induced striatal dopaminergic neurotoxicity. Co‐administration of the protein kinase C (PKC) inhibitor NPC 15437 prevented cocaine protection. At the same time, after the course of cocaine, DAT density was reduced in the plasma membrane and increased in the endosome fraction, and this effect was prevented by NPC 15437. The course of cocaine potentiated the MDMA‐induced increase in extracellular dopamine and locomotor activity, following challenge 4 days later, compared with those pretreated with saline.Conclusions and implications: Repeated cocaine treatment followed by withdrawal protected against MDMA‐induced dopaminergic neurotoxicity by internalizing DAT via a mechanism which may involve PKC. Furthermore, repeated cocaine followed by withdrawal induced behavioural and neurochemical sensitization to MDMA, measures which could be indicative of increased rewarding effects of MDMA.
NS309 restores EDHF‐type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats
Authors: Brøndum E , Kold‐Petersen H , Simonsen U , Aalkjaer C 
Published: December 2009

Background and purpose:  The endothelium‐derived hyperpolarizing factor (EDHF)‐type relaxation in mesenteric small arteries from 21 week old Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats was investigated using (6,7‐dichloro‐1H‐indole‐2,3‐dione 3‐oxime) (NS309), a potent activator of small‐conductance, calcium‐activated potassium channel (SKCa) and intermediate‐conductance, calcium‐activated potassium channel (IKCa).Experimental approach:  In the presence of inhibitors of cyclooxygenase and nitric oxide synthase [indomethacin and Nω‐nitro‐L‐arginine methyl ester (l‐NAME), respectively], acetylcholine (ACh)‐induced hyperpolarization and EDHF‐type relaxation were investigated under isometric conditions in the wire myograph using 0.5 and 1 µM NS309 and/or selective blockers of SKCa and IKCa channels. Membrane potential was recorded with glass microelectrodes, and changes in the intracellular calcium concentration of endothelial cells were visualized by confocal microscopy. SKCa expression was assessed by Western blotting.Key results:  In arteries from ZDF rats, ACh‐induced relaxation and membrane hyperpolarization were attenuated and, compared with arteries from ZL rats, NS309 was less potent at causing relaxation. Incubation with 0.5 µM NS309 did not increase ACh‐induced relaxation in arteries from ZDF rats significantly. However, 1 µM NS309 restored it (both in the absence and in the presence of indomethacin and l‐NAME) without changing endothelial intracellular calcium concentration. The restored EDHF‐type relaxation was more sensitive to TRAM‐34 (1‐[(2‐chlorophenyl) diphenylmethyl]‐1H‐pyrazole) (1 µM) than to apamin. Expression of the SKCa channel was unaltered.Conclusions and implications:  The attenuated EDHF‐type relaxation in mesenteric small arteries from ZDF rats can be restored by NS309 without changes in the intracellular calcium concentration of endothelial cells. These results may have clinical implications for the treatment of endothelial dysfunction in overweight type 2 diabetic patients.
Advances in imaging of new targets for pharmacological intervention in stroke: real‐time tracking of T‐cells in the ischaemic brain
Authors: Ortolano F , Maffia P , Dever G , Rodolico G , Millington OR , De Simoni MG , Brewer JM , Bushell TJ , Garside P , Carswell HV 
Published: December 2009

Background and purpose:  T‐cells may play a role in the evolution of ischaemic damage and repair, but the ability to image these cells in the living brain after a stroke has been limited. We aim to extend the technique of real‐time in situ brain imaging of T‐cells, previously shown in models of immunological diseases, to models of experimental stroke.Experimental approach:  Male C57BL6 mice (6–8 weeks) (n= 3) received a total of 2–5 × 106 carboxyfluorescein diacetate succinimidyl ester (CFSE)‐labelled lymphocytes from donor C57BL6 mice via i.v. injection by adoptive transfer. Twenty‐four hours later, recipient mice underwent permanent left distal middle cerebral artery occlusion (MCAO) by electrocoagulation or by sham surgery under isoflurane anaesthesia. Female hCD2‐green fluorescent protein (GFP) transgenic mice that exhibit GFP‐labelled T‐cells underwent MCAO. At 24 or 48 h post‐MCAO, a sagittal brain slice (1500 µm thick) containing cortical branches of the occluded middle cerebral artery (MCA) was dissected and used for multiphoton laser scanning microscopy (MPLSM).Key results:  Our results provide direct observations for the first time of dynamic T‐cell behaviour in living brain tissue in real time and herein proved the feasibility of MPLSM for ex vivo live imaging of immune response after experimental stroke.Conclusions and Implications:  It is hoped that these advances in the imaging of immune cells will provide information that can be harnessed to a therapeutic advantage.This article is part of a themed section on Imaging in Pharmacology. To view the editorial for this themed section visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00685.x
Modulatory effects of neuropsychopharmaca on intracellular pH of hippocampal neuronesin vitro
Authors: Bonnet Udo , Bingmann Dieter , Wiltfang Jens , Scherbaum Norbert , Wiemann Martin 
Published: December 2009

Background and purpose: The intracellular pH (pHi) of neurones is tightly regulated by, for example, membrane‐bound acid‐exchangers and loaders. Nevertheless, excessive bioelectric activity lowers steady‐state pHi. In turn, even a moderate acidification can inhibit neuronal activity, a process believed to be part of a negative feedback loop controlling neuronal excitation. As moclobemide, an antidepressant, and also some antiepileptic drugs can reduce neuronal pHi in hippocampus slicesin vitro, we screened a panel of currently used neuropsychopharmaca for comparable effects.Experimental approach: BCECF‐AM loaded hippocampal slices were superfused with 16 different neuroleptics, antidepressants and antiepileptics under bicarbonate‐buffered conditions. Changes in steady‐state pHi of CA3 neurones were measured fluorometrically.Key results: The antipsychotics haloperidol, clozapine, ziprasidone, and the antidepressants amitriptyline, doxepin, trimipramine, citalopram, mirtazapine, as well as the anticonvulsive drug tiagabine reversibly reduced the steady‐state pHi by up to 0.35 pH‐units in concentrations of 5–50 µM. In contrast, venlafaxine, the anticonvulsants carbamazepine, clonazepam, gabapentin, lamotrigine, zonisamide, and the mood stabilizer lithium had no effect on neuronal pHi.Conclusion and implications: These data substantiate the view that clinically relevant concentrations of neuroleptics and antidepressants can mediate changes in neuronal pHi, which may contribute to their pharmacological mode of action. Effects on pHi should be taken into account when therapeutic or even harmful effects of these drugs are evaluated.