bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pentameric concatenated (α4)2(β2)3 and (α4)3(β2)2 nicotinic acetylcholine receptors: subunit arrangement determines functional expression
Authors: Carbone A‐L , Moroni M , Groot‐Kormelink P‐J , Bermudez I 
Published: February 2009

Background and purpose:  α4 and β2 nicotinic acetylcholine (ACh) receptor subunits expressed heterologously in Xenopus oocytes assemble into a mixed population of (α4)2(β2)3 and (α4)3(β2)2 receptors. In order to express these receptors separately in heterologous systems, we have engineered pentameric concatenated (α4)2(β2)3 and (α4)3(β2)2 receptors.Experimental approach:  α4 and β2 subunits were concatenated by synthetic linkers into pentameric constructs to produce either (α4)2(β2)3 or (α4)3(β2)2 receptors. Using two‐electrode voltage‐clamp techniques, we examined the ability of the concatenated constructs to produce functional expression in Xenopus oocytes. Functional constructs were further characterized in respect to agonists, competitive antagonists, Ca2+ permeability, sensitivity to modulation by Zn2+ and sensitivity to up‐regulation by chaperone protein 14‐3‐3.Key results:  We found that pentameric concatamers with a subunit arrangement of β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 were stable and functional in Xenopus oocytes. By comparison, when α4 and β2 were concatenated with a subunit order of β2_β2_α4_β2_α4 or β2_α4_α4_β2_α4, functional expression in Xenopus oocytes was very low, even though the proteins were synthesized and stable. Both β2_α4_β2_α4_β2 and β2_α4_β2_α4_α4 concatamers recapitulated the ACh concentration response curve, the sensitivity to Zn2+ modulation, Ca2+ permeability and the sensitivity to up‐regulation by chaperone protein 14‐3‐3 of the corresponding non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively. Using these concatamers, we found that most α4β2‐preferring compounds studied, including A85380, 5I‐A85380, cytisine, epibatidine, TC2559 and dihydro‐β‐erythroidine, demonstrate stoichiometry‐specific potencies and efficacies.Conclusions and implications:  We concluded that the α4β2 nicotinic ACh receptors produced with β2_α4_β2_α4_β2 or β2_α4_β2_α4_α4 pentameric constructs are valid models of non‐linked (α4)2(β2)3 and (α4)3(β2)2 receptors respectively.
Synthetic and plant‐derived cannabinoid receptor antagonists show hypophagic properties in fasted and non‐fasted mice
Authors: Riedel Gernot , Fadda Paola , McKillop‐Smith Susan , Pertwee Roger G , Platt Bettina , Robinson Lianne 
Published: February 2009

Background and purpose:  Obesity is a severe health problem in the modernized world and understanding the central nervous mechanisms underlying food‐seeking behaviour and reward are at the forefront of medical research. Cannabinoid receptors have proven an efficient target to suppress hunger and weight gain by their pharmacological inactivation.Experimental approach:  A standard fasted protocol and a novel long‐term home‐cage observation system with free‐feeding animals were used to assess the feeding behaviour of mice treated with the CB1 antagonist AM251. Similarly, the effects of the phytocannabinoid Δ9‐tetrahydrocannabivarin (Δ9‐THCV), which behaves like a CB1 antagonist, were also determined in free‐feeding animals.Key results:  AM251 suppressed food intake and weight gain in fasted and non‐fasted animals. The suppression of food intake by AM251 (10 mg·kg−1) endured for a period of 6–8 h when administered acutely, and was continuous when injected for four consecutive days. Pure Δ9‐THCV also induced hypophagia and weight reduction at doses as low as 3 mg·kg−1. No rebound was observed on the following day with all drug groups returning to normal activity and feeding regimes. However, a Δ9‐THCV‐rich cannabis‐extract failed to suppress food intake and weight gain, possibly due to residual Δ9‐tetrahydrocannabinol (Δ9‐THC) in the extract. This Δ9‐THC effect was overcome by the co‐administration of cannabidiol.Conclusions and implications:  The data strongly suggest (i) the long‐term home‐cage observation system is a sensitive and obesity‐relevant tool, and (ii) the phytocannabinoid Δ9‐THCV is a novel compound with hypophagic properties and a potential treatment for obesity.
Quantitative analysis of the loss of muscarinic receptors in various peripheral tissues in M1–M5receptor single knockout mice
Authors: Ito Yoshihiko , Oyunzul Luvsandorj , Seki Masanao , Fujino (Oki) Tomomi , Matsui Minoru , Yamada Shizuo 
Published: February 2009

Background and purpose: To compare loss in binding to muscarinic receptor (mAChR) subtypes with their known functions, the total density of muscarinic receptors was measured in peripheral tissues from wild type (WT) and mAChR knockout (KO) mice.Experimental approach: Binding parameters of [N‐methyl‐3H]scopolamine methyl chloride ([3H]NMS) were determined in 10 peripheral tissues of WT and M1–M5receptor KO mice. Competition between [3H]NMS and darifenacin (selective M3receptor antagonist) was also measuredKey results: There was an extensive loss of [3H]NMS‐binding sites (maximal number of binding sites,Bmax) in heart and smooth muscle from M2KO mice, compared with WT mice. Smooth muscle from M3KO mice also showed a moderate loss ofBmax.Bmaxfell in pancreas and bladder of M4KO mice and in prostate in M1KO and M3KO mice. There was a large loss ofBmaxin exocrine and endocrine glands of M3KO mice with a moderate decrease in M2KO mice. Darifenacin inhibited specific [3H]NMS binding in submandibular gland and bladder of WT, M2KO and M3KO mice.Ki(inhibition constant) values for darifenacin in the submandibular gland were the same in WT and M2KO mice but increased in M3KO mice. However,Kivalues in bladder were decreased in M2KO mice and increased in M3KO mice.Conclusions and implications: Single mAChR KO mice exhibit a loss of mAChR in peripheral tissues that generally paralleled the reported loss of function. Quantitative analysis of data, however, also suggested that, in some instances, normal expression of a receptor subtype depended on expression of other subtypes.
Roles of purines in synaptic modulation evoked by hypercapnia in isolated spinal cord of neonatal ratin vitro
Authors: Otsuguro K , Ban M , Ohta T , Ito S 
Published: February 2009

Background and purpose: The purine compounds, adenosine 5′‐triphosphate (ATP) and adenosine, are known to accumulate in the extracellular space and to elicit various cellular responses during hypoxia/ischemia, whereas the roles of purines during hypercapnia are poorly understood. In this study, we examined the effects of various drugs affecting purine turnover on the responses to hypercapnia in the spinal cord.Experimental approach: Electrically evoked reflex potentials were measured in anin vitropreparation of the isolated spinal cord of the neonatal rat by extracellular recording. Extracellular adenosine concentrations were assayed by high performance liquid chromatography (HPLC) methods.Key results: Hypercapnia (20% CO2) depressed the reflex potentials, which were partially reversed by an adenosine A1receptor antagonist, 8‐cyclopentyl theophylline, but not by a P2 receptor antagonist, pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid. Exogenous adenosine and ATP also depressed the reflex potentials via adenosine A1receptors. The hypercapnia‐evoked depression was not reversed by inhibitors of gap junction hemichannels, anion channels, P2X7receptors or equilibrative nucleoside transporters, all of which might be involved in purine efflux pathways. The adenosine accumulation evoked by hypercapnia was not inhibited by tetrodotoxin, ethylene glycol‐bis(β‐amino ethyl ether) tetraacetic acid (EGTA) or an ecto‐ATPase inhibitor, ARL 67156. Homocysteine thiolactone, used to trap intracellular adenosine, significantly reduced extracellular adenosine accumulation during hypercapnia.Conclusions and implications: These results suggest that hypercapnia released adenosine itself from intracellular sources, using pathways different from the conventional exocytotic mechanism, and that this adenosine depressed spinal synaptic transmission via adenosine A1receptors.
Effect of tumour necrosis factor‐α and irradiation alone or in combination on the viability of hepatocellular and biliary adenocarcinoma cell lines in vitro
Authors: Qesaraku Blendi , Dudas Joszef , Rave‐Fränk Margret , Hess Clemens Friedrich , Ramadori Giuliano , Saile Bernhard , Christiansen Hans 
Published: February 2009

AbstractBackground: Tumour necrosis factor α (TNF‐α) may exhibit antitumoral activity and can influence the reaction of both tumour and normal tissue to radiation.Aims: To test the effect of TNF‐α and/or irradiation on hepatocellular (HepG2, Hep3B, Sk‐Hep1, HuH7) and cholangiocellular (Sk‐chA1, Mz‐chA1) tumour cell lines.Methods: Colony formation, apoptosis analysis and trypan blue exclusion were used to assess cell viability. Doses of radiation (2–25 Gy) and TNF‐α (100–50 000 U) as well as their respective sequencing were varied (24 and 12 h before and 6 h after). The expression of TNF‐α and TNF receptors 1/2 was determined using real‐time polymerase chain reaction and IκBα protein expression was detected by Western blot.Results: Sole irradiation induced a reduction in colony formation in all cell lines and sole TNF‐α in HepG2 and Sk‐chA1 cells only. No difference in apoptosis induction after TNF‐α or irradiation was observed. Cellular death induced by the combination of TNF‐α and radiation was not superior to the use of any of the two agents alone. All cell lines revealed that radiation induced upregulation of TNF‐α whereas the extent of TNF receptor‐specific transcription did not change. Furthermore, radiation‐induced changes in IκBα expression were not detectable.Conclusions: Our data suggest that both TNF‐α and radiation may be treatment options for hepatocellular and cholangiocellular carcinomas. Because TNF‐α and radiation do not interact in terms of radiosensitization, anti‐TNF‐α treatment may have the potential to protect against hepatocellular injury after abdominal irradiation. However, further in vivo studies are needed to confirm that anti‐TNF‐α treatment does not compromise tumour control and actually attenuates radiation‐induced liver injury.
Incontinentia Pigmenti with a Foreshortened Hand: Evidence for the Significance of NFκB in Human Morphogenesis
Authors: Kmetz Emily C. , Shashidhar Pai Gurpur , Burges Gene E. 
Published: February 2009

Abstract: The X‐linked disorder incontinentia pigmenti (IP) with its well‐defined underlying defect in the NFκB essential modulator (NEMO) gene and its variability in patients' phenotypes offers an excellent opportunity for expanding knowledge of the function of the NFκB pathway. We report a patient with the classic clinical and histologic characteristics of incontinentia pigmenti in the skin accompanied by foreshortening of the left hand. The occurrence of this limb deformity associated with a reduced expression of NFκB confirms the importance of this transcription factor in normal limb morphogenesis and may support its involvement in sonic hedgehog signaling. Further studies in established animal models may help to further define these roles.
Primary giant cell tumor of soft tissue of the groin – a case of 46 years duration
Authors: Boneschi Vinicio , Parafioriti Antonina , Armiraglio Elisabetta , Gaiani Francesca , Brambilla Lucia 
Published: February 2009

Background: Soft tissue giant cell tumor (GCT‐ST) of low malignant potential is an uncommon neoplasm, considered the soft tissue counterpart of giant cell tumor of bone. GCT‐ST mainly affects young to middle‐age adults and presents as a painless growing mass mainly located in the lower extremities and trunk. Histologically, this tumor is characterized by a mixture of uniformly scattered osteoclast‐like multinucleated giant cells intimately admixed with short fascicles of spindled cells. Complete excision with negative surgical margins is associated with a benign clinical course in most cases.Methods: The authors report the clinicopathological and immunohistochemical features of an unusual GCT‐ST of 46 years duration previously histologically misdiagnosed as Kaposi's sarcoma.Results: Histologically, the tumor was characterized by a multinodular growth pattern with osteoclast‐like multinucleated giant cells admixed with spindle cells partially arranged in a storiform pattern, fibrosis and foci of haemorrhage and mature bone. Immunohistochemistry revealed CD68 reactivity of the multinucleated giant cells.Conclusion: GCT‐ST is a rare neoplasm characterized by benign clinical course if excised adequately, as shown by our case of exceptionally long duration. Emphasis is placed on the importance of differential diagnosis with other giant cell‐rich soft tissue neoplasms because clinical behaviour, prognosis and treatment significantly differ.
Obesity‐associated lymphoedematous mucinosis
Authors: Rongioletti Franco , Donati Pietro , Amantea Ada , Ferrara Gerardo , Montinari Martina , Santoro Francesca , Parodi Aurora 
Published: February 2009

Background: Mucin deposition on the shins is considered as an indicator of pretibial myxoedema, which is typically seen in patients with Graves’ disease.Objective: The purpose of this study was to report the clinical and histopathological features of a group of patients with pretibial mucinosis in the absence of thyroid disease.Methods: Five patients are included in this series and studied both clinically and histologically and compared with similar cases in the literature.Results: All patients were middle aged or elderly. Four patients were women. They were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema sparing the feet. Semitranslucent papules and/or nodules and sometimes vesicles were found on the shins. Characteristic histological features include (i) hyperorthokeratosis with epidermal atrophy and effacement of the rete ridge pattern, (ii) oedema in the papillary and upper part of the reticular dermis with mucin deposition stained positively with alcian blue and colloidal iron, (iii) angioplasia in the upper part of dermis with upward‐running, increased and thickened capillary vessels and (iv) variable fibrosis in the reticular dermis with separation of collagen bundles and increased stellate or linear fibroblasts. A hypocaloric diet was given in two cases, and an important weight loss was observed, which was accompanied by a marked improvement of the pretibial mucinosis.Conclusions: Pretibial mucinosis is a histological feature associated with morbid obesity and lymphoedematous features of the legs that should be distinguished from true pretibial myxoedema. The term of ‘obesity‐associated lymphoedematous mucinosis’ seems to be appropriate for this condition.
Anti‐leukemic activity of valproic acid and imatinib mesylate on human Ph+ ALL and CML cells in vitro
Authors: Kircher Brigitte , Schumacher Petra , Petzer Andreas , Hoflehner Elisabeth , Haun Margot , Wolf Anna Maria , Nachbaur David , Gastl Günther 
Published: February 2009

AbstractThe armamentarium of anti‐leukemic drugs has increased substantially since anti‐leukemic activities were recently found for a variety of non‐classical cytostatic drugs, among them the histone deacetylase (HDAC) inhibitor valproic acid (VPA). This study investigated the effect of VPA on proliferation and apoptosis of human Philadelphia chromosome‐positive (Ph+) acute lymphatic (ALL) and chronic myeloid leukemia (CML) cells and on colony formation of human chronic‐phase CML progenitor cells. Strong anti‐proliferative and pro‐apoptotic effects of VPA were observed on human ALL and CML cell lines at concentrations achievable in vivo. These effects were most pronounced in ALL cell lines as well as in primary ALL cells. Notably, VPA revealed enhanced activity with imatinib mesylate, nilotinib, the farnesyl transferase inhibitor SCH66336, interferon‐alpha and cytosine arabinoside. VPA inhibited the growth of colony‐forming cells from 12 Ph+ chronic‐phase CML patients but also of those from normal healthy controls in a dose‐dependent fashion. HDAC‐inhibiting activity of VPA was confirmed on ALL and CML cells. In conclusion, VPA, whether alone or in combination with other non‐classical anti‐leukemic compounds, exerts significant anti‐leukemic effects on human ALL and CML cells.
EFFECT OF OXYGEN CONCENTRATION ON THE BIOCHEMICAL AND CHEMICAL CHANGES OF STORED LONGAN FRUIT
Authors: CHENG G. , JIANG Y. , DUAN X. , MACNISH A. , YOU Y. , LI YUEBIAO 
Published: February 2009

ABSTRACT Longan fruits were stored for 6 days in atmosphere of 5, 21 (air) or 60% O2 (balance N2) at 28C and 90–95% relative humidity to examine effects of low and high O2 concentration on enzymatic browning and quality attributes of the fruit. Changes in pericarp browning, pulp breakdown, disease development, total phenol content, activities of phenol metabolism‐associated enzymes, relative leakage rate, α,α‐diphenyl‐β‐picrylhydrazy (DPPH) radical scavenging activity, and contents of total soluble solids, titratable acidity and ascorbic acid were evaluated. Storage of fruit in a 5% O2 atmosphere markedly delayed pericarp browning in association with maintenance of high total phenolic content and reduced activities of polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia lyase. Moreover, the fruit stored in a 5% O2 atmosphere exhibited a lower relative leakage rate and higher DPPH radical scavenging activity than fruit stored in air. This presumably was beneficial in maintaining compartmentation of enzymes and substrates, and thus, reducing pericarp browning. Pulp breakdown and disease development were also reduced by exposure to a 5% oxygenatmosphere. On the contrary, exposure of longan fruit to a 60% O2 atmosphere accelerated pericarp browning, pulp breakdown and decay development. PPO and POD activities and relative leakage rate were similar for control and 60% O2‐treated fruit after 4 and 6 days of storage. Furthermore, treatment with 60% O2 significantly decreased the phenolic content and DPPH scavenging activity of fruit. In addition, exposure to 5 or 60% O2 resulted in a higher level of total soluble solids, but a lower level of ascorbic acid of longan fruit flesh. In conclusion, exposure to a 5% O2 atmosphere showed great potential to reduce pericarp browning and extend shelf life of longan fruit.PRACTICAL APPLICATIONSPericarp browning and pulp breakdown are the major causes of deterioration in postharvest longan. Conventional controlled atmosphere with low O2 and high CO2 is effective in maintaining quality and extending shelf life of fruits and vegetables, including inhibition of tissue browning. In this study, 5%‐controlled atmosphere reduced significantly pericarp browning, pulp breakdown and rot development. It could potentially be useful as a postharvest technology of longan fruit for reducing or replacing the use of chemicals such as SO2 and fungicides, but it requires further investigation.
RESPONSE OF 1‐METHYLCYCLOPROPENE TREATED “GRANNY SMITH” APPLE FRUIT TO AIR AND CONTROLLED ATMOSPHERE STORAGE CONDITIONS
Authors: AKBUDAK B. , OZER M.H. , ERTURK U. , CAVUSOGLU S. 
Published: February 2009

ABSTRACT In the study, the efficacy of 1‐Methylcyclopropene (1‐MCP) on the quality of apples cv. “Granny Smith” was examined. Fruits were stored for 120 and 180 days at 0 ± 0.5C and 90 ± 5% relative humidity (RH) under normal (NA) and controlled atmosphere (CA), and samples taken at 120 and 180 days of storage were kept at 20 ± 2C and 60 ± 5% RH for 7 days. Weight loss was higher in fruits stored under NA. The lowest respiration rates were in CA while the highest rates were found in NA‐stored fruits without pretreated. 1‐MCP + CA reduced the internal ethylene concentration from 10.63 µL/L to 0.60 µL. The incidence and severity of superficial scald was 68.10 and 77.00% in fruits stored in NA. 1‐MCP consistently suppressed the expression of superficial scald. 1‐MCP maintained the quality fruit kept in CA and NA environments to a higher degree than nontreated apples over a 180‐day storage period. The results indicated that cv. “Granny Smith” could be stored successfully under 1‐MCP + CA conditions and that 1‐MCP + NA may be a viable alternative to CA for optimal eating quality.PRACTICAL APPLICATIONS1‐Methylcyclopropene (1‐MCP) is an effective inhibitor of ethylene action and it binds irreversibly to ethylene receptors. 1‐MCP delays the onset of the climacteric ripening of fruits. Recently research has been conducted on the effects of 1‐MCP on postharvest behavior of fruits and vegetables with the objective of reducing physiological disorders and quality losses to prolong their commercial life. The use of 1‐MCP is easy. It is important that the fruit treated with 1‐MCP reach a good sensory quality at the commercial level. Superficial scald of apples is a physiological disorder, which following long‐term storage has the potential to destroy the market value and utility of millions of tons of fresh apples annually. The present work evaluated a prestorage conditioning treatment to protect against this physiological disorder. Results will allow the long storage of apple cv. “Granny Smith,” benefiting growers, exporters, shippers and distributors of this horticultural product.
CHANGES IN QUALITY ATTRIBUTES OF LONGAN JUICE DURING STORAGE IN RELATION TO EFFECTS OF THERMAL PROCESSING
Authors: LI J. , MIAO S. , JIANG Y. 
Published: February 2009

ABSTRACT Longan juice is accepted gradually by consumers due to its unique succulent, sweet and aromatic flavor. The effects of thermal processing (91C, 20 min) on quality related attributes (color, translucency, total soluble solids, total acidity, reducing sugars, ascorbic acid, phenolic compounds, protein and pectin) of longan juice during storage at low temperature were investigated. The heat‐treated longan juice had a higher translucency and lower concentrations of pectin, phenolic compounds and proteins of longan juice, compared with the nonheat‐treated juice. Furthermore, the thermal processing maintained higher concentrations of total soluble solids and total acidity but a lower ascorbic acid concentration. However, the thermal processing had no significant effects on reducing sugar concentration. Overall, the thermal processing maintained effectively color appearance and nutritional attributes such as total soluble solids and total acidity of longan juice during storage at low temperature. These results suggest that the thermal processing exhibits a potential for quality maintenance of longan juice. PRACTICAL APPLICATIONSBrowning and turbidity are the major factor to influence quality of fruit juice during storage. Thermal processing is generally applied to improve quality and extend shelf life of fruit‐related products. In this study, application of thermal processing exhibited potential for quality maintenance of longan juice in terms of evaluations of color, translucency and concentrations of total soluble solids, total acidity, reducing sugars, ascorbic acid, phenolic compounds, protein and pectin. The information obtained from this study could be used as a guideline for designing thermal processing to control the quality of longan juice.