bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effector and scaffolding proteins AF6 and MUPP1 interact with connexin36 and localize at gap junctions that form electrical synapses in rodent brain
Authors: Li X. , Lynn B. D. , Nagy J. I. 
Published: December 2011

AbstractElectrical synapses formed by neuronal gap junctions composed of connexin36 (Cx36) occur in most major structures in the mammalian central nervous system. These synapses link ensembles of neurons and influence their network properties. Little is known about the macromolecular constituents of neuronal gap junctions or how transmission through electrical synapses is regulated at the level of channel conductance or gap junction assembly/disassembly. Such knowledge is a prerequisite to understanding the roles of gap junctions in neuronal circuitry. Gap junctions share similarities with tight and adhesion junctions in that all three reside at close plasma membrane appositions, and therefore may associate with similar structural and regulatory proteins. Previously, we reported that the tight junction‐associated protein zonula occludens‐1 (ZO‐1) interacts with Cx36 and is localized at gap junctions. Here, we demonstrate that two proteins known to be associated with tight and adherens junctions, namely AF6 and MUPP1, are components of neuronal gap junctions in rodent brain. By immunofluorescence, AF6 and MUPP1 were co‐localized with Cx36 in many brain areas. Co‐immunoprecipitation and pull‐down approaches revealed an association of Cx36 with AF6 and MUPP1, which required the C‐terminus PDZ domain interaction motif of Cx36 for interaction with the single PDZ domain of AF6 and with the 10th PDZ domain of MUPP1. As AF6 is a target of the cAMP/Epac/Rap1 signalling pathway and MUPP1 is a scaffolding protein that interacts with CaMKII, the present results suggest that AF6 may be a target for cAMP/Epac/Rap1 signalling at electrical synapses, and that MUPP1 may contribute to anchoring CaMKII at these synapses.
AMPA receptor modulation by cornichon‐2 dictated by transmembrane AMPA receptor regulatory protein isoform
Authors: Gill Martin B. , Kato Akihiko S. , Wang He , Bredt David S. 
Published: December 2011

AbstractTransmembrane AMPA receptor regulatory proteins (TARPs) are auxiliary subunits that modulate AMPA receptor trafficking, gating and pharmacology throughout the brain. Why cornichon‐2 (CNIH‐2), another AMPA receptor‐associated protein, modulates AMPA receptor gating and pharmacology in hippocampal neurons but not cerebellar granule neurons remains unresolved. Here, we report that CNIH‐2 differentially impacts Type‐Ia (γ‐2 or γ‐3) vs. Type‐Ib (γ‐4 or γ‐8) TARP‐containing AMPA receptors. Specifically, with AMPA receptors comprising γ‐2, the cerebellar‐enriched TARP isoform, CNIH‐2 decreases IKA/IGlu ratio and decreases cyclothiazide efficacy while having minimal impact on recovery from desensitization and deactivation kinetics. By contrast, with AMPA receptors comprising γ‐8, the hippocampal‐enriched TARP isoform, we find that CNIH‐2 slows deactivation kinetics, increases cyclothiazide potency and occludes a novel AMPA receptor kinetic phenomenon, namely resensitization. Additionally, we find that CNIH‐2 differentially modulates the glutamate off‐kinetics of γ‐8‐containing, but not γ‐2‐containing, AMPA receptors in a manner dependent upon the duration of agonist application. Together, these data demonstrate that the modulation of AMPA receptors by CNIH‐2 depends upon the TARP isoform composition within the receptor complex.
Striatal NTS1, dopamine D2 and NMDA receptor regulation of pallidal GABA and glutamate release – a dual‐probe microdialysis study in the intranigral 6‐hydroxydopamine unilaterally lesioned rat
Authors: Ferraro Luca , O’Connor William T. , Beggiato Sarah , Tomasini Maria C. , Fuxe Kjell , Tanganelli Sergio , Antonelli Tiziana 
Published: December 2011

AbstractThe current microdialysis study elucidates a functional interaction between the striatal neurotensin NTS1 receptor and the striatal dopamine D2 and N‐methyl‐d‐aspartic acid (NMDA) receptors in the regulation of striatopallidal gamma‐aminobutyric acid (GABA) and glutamate levels after an ipsilateral intranigral 6‐hydroxydopamine‐induced lesion of the ascending dopamine pathways to the striatum. Lateral globus pallidus GABA levels were higher in the lesioned group while no change was observed in striatal GABA and glutamate levels. The 6‐hydroxydopamine‐induced lesion did not alter the ability of intrastriatal NT (10 nm) to counteract the decrease in pallidal GABA and glutamate levels induced by the dopamine D2‐like receptor agonist quinpirole (10 μm). A more pronounced increase in the intrastriatal NMDA‐ (10 μm) induced increase in pallidal GABA levels was observed in the lesioned group while it attenuated the increase in striatal glutamate levels and amplified the increase in pallidal glutamate levels compared with that observed in the controls. NT enhanced the NMDA‐induced increase in pallidal GABA and glutamate and striatal glutamate levels; these effects were counteracted by the NTS1 antagonist SR48692 (100 nm) in both groups. These findings demonstrate an inhibitory striatal dopamine D2 and an excitatory striatal NMDA receptor regulation of striatopallidal GABA transmission in both groups. These actions are modulated by NT via antagonistic NTS1/D2 and facilitatory NTS1/NMDA receptor–receptor interactions, leading to enhanced glutamate drive of the striatopallidal GABA neurons associated with motor inhibition, effects which all are counteracted by SR48692. Thus, NTS1 antagonists in combination with conventional treatments may provide a novel therapeutic strategy in Parkinson’s disease.
Differential effects of brain‐derived neurotrophic factor and neurotrophin‐3 on hindlimb function in paraplegic rats
Authors: Boyce Vanessa S. , Park Jihye , Gage Fred H. , Mendell Lorne M. 
Published: December 2011

AbstractWe compared the effect of viral administration of brain‐derived neurotrophic factor (BDNF) or neurotrophin 3 (NT‐3) on locomotor recovery in adult rats with complete thoracic (T10) spinal cord transection injuries, in order to determine the effect of chronic neurotrophin expression on spinal plasticity. At the time of injury, BDNF, NT‐3 or green fluorescent protein (GFP) (control) was delivered to the lesion via adeno‐associated virus (AAV) constructs. AAV–BDNF was significantly more effective than AAV–NT‐3 in eliciting locomotion. In fact, AAV–BDNF‐treated rats displayed plantar, weight‐supported hindlimb stepping on a stationary platform, that is, without the assistance of a moving treadmill and without step training. Rats receiving AAV–NT‐3 or AAV–GFP were incapable of hindlimb stepping during this task, despite provision of balance support. AAV–NT‐3 treatment did promote the recovery of treadmill‐assisted stepping, but this required continuous perineal stimulation. In addition, AAV–BDNF‐treated rats were sensitized to noxious heat, whereas AAV–NT‐3‐treated and AAV–GFP‐treated rats were not. Notably, AAV–BDNF‐treated rats also developed hindlimb spasticity, detracting from its potential clinical applicability via the current viral delivery method. Intracellular recording from triceps surae motoneurons revealed that AAV–BDNF significantly reduced motoneuron rheobase, suggesting that AAV–BDNF promoted the recovery of over‐ground stepping by enhancing neuronal excitability. Elevated nuclear c‐Fos expression in interneurons located in the L2 intermediate zone after AAV–BDNF treatment indicated increased activation of interneurons in the vicinity of the locomotor central pattern generator. AAV–NT‐3 treatment reduced motoneuron excitability, with little change in c‐Fos expression. These results support the potential for BDNF delivery at the lesion site to reorganize locomotor circuits.
Right–left asymmetry in the cortical processing of sounds for social communication vs. navigation in mustached bats
Authors: Kanwal Jagmeet S. 
Published: December 2011

AbstractIn the Doppler‐shifted constant frequency processing area in the primary auditory cortex of mustached bats,Pteronotus parnellii, neurons respond to both social calls and to echolocation signals. This multifunctional nature of cortical neurons creates a paradox for simultaneous processing of two behaviorally distinct categories of sound. To test the possibility of a stimulus‐specific hemispheric bias, single‐unit responses were obtained to both types of sounds, calls and pulse‐echo tone pairs, from the right and left auditory cortex. Neurons on the left exhibited only slightly higher peak response magnitudes for their respective best calls, but they showed a significantly higher sensitivity (lower response thresholds) to calls than neurons on the right. On average, call‐to‐tone response ratios were significantly higher for neurons on the left than for those on the right. Neurons on the right responded significantly more strongly to pulse‐echo tone pairs than those on the left. Overall, neurons in males responded to pulse‐echo tone pairs with a much higher spike count compared to females, but this difference was less pronounced for calls. Multidimensional scaling of call responses yielded a segregated representation of call types only on the left. These data establish for the first time, a behaviorally directed right–left asymmetry at the level of single cortical neurons. It is proposed that a lateralized cortex emerges from multiparametric integration (e.g. combination‐sensitivity) within a neuron and inhibitory interactions between neurons that come into play during the processing of complex sounds.
The traditional ayurvedic medicine, Eugenia jambolana (Jamun fruit), decreases liver inflammation, injury and fibrosis during cholestasis
Authors: Donepudi Ajay C. , Aleksunes Lauren M. , Driscoll Maureen V. , Seeram Navindra P. , Slitt Angela L. 
Published: December 2011

AbstractBackgroundCholestasis is a common disease of the liver. Chronic cholestasis eventually leads to hepatic cirrhosis and fibrosis, and rodent chronic cholestasis models are used to study aspects of fibrosis and cirrhosis. Cholestasis‐induced liver injury and fibrosis are associated with increased oxidative stress and inflammation. Few pharmacological therapies exist for treatment of cholestasis or cirrhosis, but it is known that humans with better nutritional intake are less likely to develop certain types of cirrhosis. Eugenia jambolana (Jamun) is a tropical berry fruit rich in antioxidant anthocyanin compounds.AimAs anthocyanins decrease cellular lipid peroxidation and oxidative stress, it was hypothesized that Jamun fruit extract (JFE) administration could protect against cholestatic liver injury and inflammation in mice.MethodStarting 24 h after sham or bile‐duct ligation (BDL) surgery, male C57Bl/6 mice were administered vehicle or JFE (100 mg/kg, po) for 10 days.ResultsMice that underwent BDL had elevated serum ALT levels, which were reduced to 60% by JFE treatment. Likewise, BDL caused hepatic inflammation, macrophage infiltration, fibrosis and necrosis, all of which were largely improved by JFE. Interestingly, hepatoprotection was observed in JFE‐treated BDL mice, despite suppressed transporter expression and increased hepatic bile acid concentrations.ConclusionJamun fruit phytochemicals decreased hepatic inflammation and oxidative stress, and protected against hepatocellular injury in mice. Jamun warrants further investigation as a potential antioxidant/anti‐inflammatory therapy not only to treat cholestasis but also other liver diseases with an inflammatory component.
The potential role of prebiotic fibre for treatment and management of non‐alcoholic fatty liver disease and associated obesity and insulin resistance
Authors: Parnell Jill A. , Raman Maitreyi , Rioux Kevin P. , Reimer Raylene A. 
Published: December 2011

AbstractNon‐alcoholic fatty liver disease (NAFLD) and the more severe non‐alcoholic steatohepatitis (NASH) represent a spectrum of diseases involving hepatic fat accumulation and histological features essentially identical to alcoholic liver disease; however, they occur in the absence of excessive alcohol intake. They typically arise in conjunction with one or more features of the metabolic syndrome. Lifestyle mediated weight loss remains the primary mode of therapy forNAFLDandNASH, but this is often ineffective and adjunctive medical and surgical treatments are presently lacking. Prebiotic fibres are a group of non‐digestible carbohydrates that modulate the human microbiota in a manner that is advantageous to host health. Rodent studies suggest that dietary supplementation with prebiotic fibres positively impactsNAFLDby modifying the gut microbiota, reducing body fat, and improving glucoregulation. Future research should focus on placebo‐controlled, human, clinical trials using histological endpoints to address the effects of prebiotics onNAFLDandNASH. The aim of this review is to summarize current knowledge about prebiotics as an emerging therapeutic target forNAFLD.
Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization‐autoimmune hepatitis prospective study)
Authors: Migita Kiyoshi , Watanabe Yukio , Jiuchi Yuka , Nakamura Yoko , Saito Akira , Yagura Michiyasu , Ohta Hajime , Shimada Masaaki , Mita Eiji , Hijioka Taizo , Yamashita Haruhiro , Takezaki Eiichi , Muro Toyokichi , Sakai Hironori , Nakamuta Makoto , Abiru Seigo , Komori Atsumasa , Ito Masahiro , Yatsuhashi Hiroshi , Nakamura Minoru , Ishibashi Hiromi ,   the Japanese NHO‐Liver‐network study group
Published: December 2011

AbstractBackground/AimsAlthough the outcome of autoimmune hepatitis (AIH) is generally good, the natural course and likelihood of progression to cirrhosis or hepatocellular carcinoma (HCC) remain undefined, and may vary by region and population structure. Our aims were to evaluate risk factors that contribute to poor outcome and particularly development of HCC in a prospective multicentric cohort study of AIH.MethodsThe study group comprised 193 Japanese patients with AIH who were prospectively followed up at annual intervals between 1995 and 2008. The mean follow‐up period was 8.0 ± 4.5 years.ResultsTwenty‐one (10.9%) patients had cirrhosis at presentation and a further 15 (7.8%) developed cirrhosis during the follow‐up period. Survival rates were 94.2% at 10 years and 89.3% at 15 years. HCC was diagnosed in seven of the 193 patients. The presence of cirrhosis at presentation was a risk factor for HCC according to a Cox proportional hazard model, and the HCC‐free survival rate was significantly lower in those with cirrhosis compared to those without cirrhosis according to Kaplan–Meier analysis.ConclusionsAlthough the outcome of AIH is as good if not better among Japanese than for other populations, there was an increased risk of HCC in these patients. Cirrhosis at presentation was predictive of development of HCC in AIH in Japan.
Propagation of cutaneous thermal injury: A mathematical model
Authors: Xue Chuan , Chou Ching‐Shan , Kao Chiu‐Yen , Sen Chandan K. , Friedman Avner 
Published: December 2011

AbstractCutaneous burn wounds represent a significant public health problem with 500,000 patients per year in the USA seeking medical attention. Immediately after skin burn injury, the volume of the wound burn expands due to a cascade of chemical reactions, including lipid peroxidation chain reactions. Such expansion threatens life and is therefore highly clinically significant. Based on these chemical reactions, the present paper develops for the first time a three‐dimensional mathematical model to quantify the propagation of tissue damage within 12 hours post initial burn. We use the model to investigate the effect of supplemental antioxidant vitamin E for intercepting propagation. We show, for example, that if tissue levels of vitamin E tocotrienol are increased, postburn, by five times then this would slow down the lipid peroxide propagation by at least 50%. We chose the alpha‐tocotrienol form of vitamin E as it is a potent inhibitor of 12‐lipoxygenase, which is known to propagate oxidative lipid damage. Our model is formulated in terms of differential equations, and sensitivity analysis is performed on the parameters to ensure the robustness of the results.
Congenital Erosive and Vesicular Dermatosis: A New Case and Review of the Literature
Authors: Mashiah Jacob , Wallach Daniel , Leclerc‐Mercier Stéphanie , Bodemer Christine , Hadj‐Rabia Smaïl 
Published: December 2011

Abstract:  Congenital erosive and vesicular dermatosis is a rare syndrome first described by Cohen et al in 1985. Most of the 18 cases published have been reported in premature newborns. Affected babies typically present with erosions and vesicles that tend to heal shortly after birth with reticulated scaring. We report an additional case, followed up for 5 years, in which we excluded a pathogenic mutation in the TP63 gene.
Human platelet concentrates: a source of solvent/detergent‐treated highly enriched brain‐derived neurotrophic factor
Authors: Burnouf Thierry , Kuo Ya‐Po , Blum David , Burnouf Sylvie , Su Chen‐Yao 
Published: December 2011

BACKGROUND: Human blood platelets (PLTs) contain brain‐derived neurotrophic factor (BDNF), a neurotrophin that binds to neurotrophic tropomyosin‐related kinase B (TrkB) receptor on central nervous system cells. This binding promotes neural synaptic plasticity and memory and prevents neuronal degeneration. Alterations in BDNF homeostasis are associated with aging and are found in several neurodegenerative conditions such as Alzheimer's, Huntington's, and Parkinson's diseases and multiple sclerosis. We have developed PLT viral inactivation and chromatographic fractionation processes and decided here to identify fractions enriched in BDNF.STUDY DESIGN AND METHODS: PLT concentrates (PCs) were treated by solvent/detergent (S/D), extracted by oil, and subjected to fractionation (C18, sulfopropyl [SP]‐Sepharose, diethylaminoethyl [DEAE]‐Sepharose, or activated charcoal). BDNF and pro‐BDNF were evaluated by enzyme‐linked immunosorbent assay, and Western blot. TrkB was studied by Western blot. Tri‐n‐butyl phosphate (TnBP) was quantified by high‐performance liquid chromatography, and Triton X‐45 by gas chromatography.RESULTS: The mean BDNF content of 2.9 ± 0.7 ng/mL in PC was noted to increase to 56.2 ± 2.4 ng/mL after S/D treatment and remained stable during oil extraction. Approximately 70% of the BDNF content was recovered after C18 chromatography. BDNF did not bind to DEAE‐Sepharose and was almost completely adsorbed by charcoal. Chromatography on SP‐Sepharose yielded a highly enriched 13‐kDa mature BDNF fraction that was more than 170‐fold purified, with a mean of 137 ± 29.4 ng/mL and 82% chromatographic recovery, devoid of detectable TnBP and Triton X‐45. Pro‐BDNF and TrkB proteins were not detected in the PLT extracts.CONCLUSION: We obtained a S/D‐treated, highly enriched mature PLT‐derived BDNF fraction that could help unveil the pharmacokinetics, pharmacodynamic, and potential therapeutic applications of the BDNF neurotrophin.
Cost‐effectiveness of using recombinant activated factor VII as an off‐label rescue treatment for critical bleeding requiring massive transfusion
Authors: Ho Kwok M. , Litton Edward 
Published: December 2011

BACKGROUND: Recombinant activated factor VII (rFVIIa) is widely used as an off‐label rescue treatment for patients with nonhemophilic critical bleeding.STUDY DESIGN AND METHODS: Using data from the intensive care unit, transfusion service, and death registry, the long‐term survival after using rFVIIa and the associated cost per life‐year gained in a consecutive cohort of patients with critical bleeding requiring massive transfusion (≥10 red blood cell [RBC] units in 24 hr) were assessed. rFVIIa was only used as a lifesaving treatment when conventional measures had failed.RESULTS: Of the 353 patients with critical bleeding requiring massive transfusion, 81 (23%) required rFVIIa as a lifesaving rescue treatment. The patients requiring rFVIIa received a greater number of transfusions (number of units: RBCs, 18 vs. 12; fresh‐frozen plasma, 16 vs. 10; platelets, 4 vs. 2; p < 0.001) and had a shorter survival time (24 months vs. 33 months; p = 0.002) than those who did not require rFVIIa. The total cost per life‐year gained of massive transfusion and incremental cost of rFVIIa as a lifesaving treatment were US$1,148,000 (£711,760; 95% confidence interval [CI], US$825,000‐US$1,471,000) and US$736,000 (£456,320; 95% CI, US$527,000‐US$945,000), respectively. The incremental costs of rFVIIa increased with severity of illness and transfusion requirement and were greater than the usual acceptable cost‐effective limit (<US$100,000 per life‐year) for most patients with critical bleeding.CONCLUSIONS: As a lifesaving treatment for critical bleeding, the incremental cost of rFVIIa was high. Careful patient selection is critical to balance the potential benefits of rFVIIa in an individual patient against the cost to the community.
Exploratory in vitro study of red blood cell storage containers formulated with an alternative plasticizer
Authors: Dumont Larry J. , Baker Sharry , Dumont Deborah F. , Herschel Louise , Waters Susan , Calcagni Kristin , Sandford Craig , Radwanski Katherine , Min Kyungyoon , David Raymond M. , Otter Rainer 
Published: December 2011

BACKGROUND: The plasticizer di‐2‐ethylhexyl phthalate (DEHP) is a common component in medical plastics. There is motivation to replace this component; however, DEHP is necessary to prevent excessive hemolysis in stored red blood cells (RBCs). Our objective is to evaluate a candidate replacement plasticizer (Hexamoll, di‐isononyl cyclohexane‐1,2‐dicarboxylic acid [DINCH], BASF Corp.) compared to DEHP in an in vitro feasibility study. We hypothesize that the candidate will provide at least equivalent protection against hemolysis for RBCs stored for 42 days and periodic mixing of RBCs will add additional protection against hemolysis.STUDY DESIGN AND METHODS: Whole blood was collected into citrate‐phosphate‐dextrose; combined into pools of 2 ABO identical whole blood units; and divided, leukoreduced, centrifuged, and separated into plasma and RBCs. Additive solution was added, and the RBCs were stored for 42 days at 1 to 6°C. In three parts of this study, split pools were paired as DINCH‐polyvinyl chloride (PVC) with weekly mixing versus DINCH‐PVC with no mixing, DINCH‐PVC mixed versus DEHP‐PVC no mix, and DINCH‐PVC versus DEHP‐PVC with neither mixed. A standard panel of in vitro RBC characteristics was determined on Days 0 and 42.RESULTS: Mixing DINCH‐PVC weekly improved Day 42 hemolysis (0.36 ± 0.07% vs.0.56 ± 0.15%, p = 0.002), and mixed DINCH‐PVC bags were noninferior to unmixed DEHP‐PVC bags (p ≤ 0.05). DINCH‐PVC bags stored without weekly mixing were inferior to unmixed DEHP‐PVC bags for hemolysis on Day 42, although no individual bag exceeded 0.8% hemolysis.CONCLUSION: Periodic mixing of RBCs stored in DINCH‐PVC provides additional protection against hemolysis. Unmixed DINCH‐PVC bags were inferior to DEHP‐PVC bags for prevention of hemolysis, but remain a candidate for replacement DEHP in RBC storage bags.
Light Reflection Behavior of ZrB2‐Based Composites with SiC Particles
Authors: Ikegami Masahide , Guo Shuqi , Matsumura Katsunori , Kagawa Yutaka 
Published: December 2011

The light reflection behavior of ZrB2‐based composites with SiC particles was examined in the infrared wavelength range of 1.5–20 μm and at room temperature. Effects of the amount and size of SiC particles on light reflection behavior were evaluated. The results showed that the light reflection behavior of the composites was closely linked with the light absorption of the added SiC particles, in absence of light scattering from the SiC particles. In addition, the light reflectance of the composites depended on the amount and size of the SiC particles. Increase in the amount and size of the SiC particles led to decrease in the light reflectance of the composites.