bluuebunny/crossref_metadata_2025 huggingface dataset:
CircHIPK3 regulates cardiac fibroblast proliferation, migration and phenotypic switching through the miR-152-3p/TGF-β2 axis under hypoxia
Authors: Liu Weiwei , Wang Yan , Qiu Zhimei , Zhao Ranzun , Liu Zhijiang , Chen Wenming , Ge Junbo , Shi Bei
Published: August 2020

Background

The occurrence of pathological cardiac fibrosis is attributed to tissue hypoxia. Circular RNAs play significant regulatory roles in multiple cardiovascular diseases and are involved in the regulation of physiological and pathophysiological processes. CircHIPK3 has been identified as the one of the most crucial regulators in cardiac fibrosis. However, the mechanisms by which circHIPK3 regulates cardiac fibrosis under hypoxia remain unclear. Our study aimed to determine circHIPK3 expression in cardiac fibroblasts (CFs) and investigate the functions of circHIPK3 in hypoxia environment.

Methods

The expression level of circHIPK3 in CFs under hypoxia (1% O2) was analyzed by qRT-PCR. The role of circHIPK3 on the proliferation and migration of CFs were determined by EdU, cell wound scratch assay and cell cycle. The expression of proteins associated with phenotypic transformation in CFs in vitro was examined by immunofluorescence assay and western blot. Bioinformatics analysis, dual luciferase activity assay and RNA fluorescent in situ hybridization assay revealed that miR-152-3p was identified as a target of circHIPK3 and that TGF-β2 was targeted by miR-152-3p.

Results

CircHIPK3 expression was significantly upregulated in CFs in a hypoxic environment. In vitro, overexpressing circHIPK3 obviously promoted CF proliferation, migration and phenotypic changes under hypoxia, but those processes were suppressed by circHIPK3 silencing. CircHIPK3 acted as an endogenous miR-152-3p sponge and miR-152-3p aggravated circHIPK3 silencing induced inhibition of CF proliferation, migration, phenotypic transformation and TGF-β2 expression in vitro. In summary, circHIPK3 plays a pivotal role in the development of cardiac fibrosis by targeting the miR-152-3p/TGF-β2 axis.

Conclusions

These findings demonstrated that circHIPK3 acted as a miR-152-3p sponge to regulate CF proliferation, migration and phenotypic transformation through TGF-β2, revealing that modulation of circHIPK3 expression may represent a potential target to promote the transition of hypoxia-induced CFs to myofibroblasts.
Distribution characteristics of serum β2-microglobulin between viral and bacterial lower respiratory tract infections: a retrospective study
Authors: Cai Xulong , Xu Qiaolan , Zhou Chenrong , Zhou Li , Yong Qijun , Mu Qing , Cheng Yan , Wang Jiena , Xie Jingjing
Published: August 2020

Background

Lower respiratory tract infection (LRTI) is one of the leading cause of death in children under 5 years old around the world between 1980 and 2016. Distinguishing between viral and bacterial infection is challenging when children suffered from LRTI in the absence of pathogen detection. The aim of our study is to analyze the difference of serum β2-microglobulin (β2-MG) between viral LRTI and bacterial LRTI in children.

Methods

This retrospective study included children with LRTI caused by a single pathogen from Yancheng Third People’s Hospital, Yancheng, China, between January 1, 2016 and December 31, 2019. Participants were divided into the younger group (1 year old ≤ age < 3 years old) and the older group (3 years old ≤ age < 5 years old) for subgroup analysis.

Results

A total of 475 children with LRTI caused by common respiratory pathogens were identified. In the younger group as well as the older group, the serum level of β2-MG in respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly increased compared to that in the Mycoplasma pneumoniae group. Compared with Streptococcus pneumoniae infection group, the serum β2-MG level of respiratory syncytial virus, influenza A virus and influenza B virus groups were significantly higher in children between 1 and 3 years old.

Conclusions

The serum β2-MG may distinguish viral infection from bacterial infection in children with LRTI.
Eucalyptus calidissima (Myrtaceae), a new ironbark species from the Hunter Valley of New South Wales, Australia
Authors: Bell Stephen , Klaphake Van
Published: August 2020

Eucalyptus calidissima (Myrtaceae), a new and highly restricted ironbark species from the Hunter Valley of New South Wales is described and illustrated. The new species had previously been included in E. nubilis Maiden & Blakely (syn. Eucalyptus nubila L.A.S.Johnson, orth. var.), but differs in the ribbed hypanthia, hemispherical to bluntly-conical calyptra which are shorter than the hypanthia, and the slightly larger, globular to obconical ribbed fruit. At present, E. calidissima is known only from a single population occurring across c. 200 ha and is considered rare, but it is not under immediate threat. Amendments to relevant sections of the New South Wales and Australian identification keys are provided.
Drosera stipularis, a new species for the D. petiolaris complex from Cape York Peninsula, Queensland
Authors: Baleeiro Paulo C , Jobson Richard W , Barrett Russell L
Published: August 2020

Across tropical northern Australia 14 Drosera species are recognised within the D. petiolaris complex. The complex is placed in section Lasiocephala; a group of perennial sundews mostly characterised by an indumentum of white hairs upon the petiole. Here we describe a new species for the complex, D. stipularis

Baleeiro, R.W.Jobson & R.L.Barrett, which is known only from white-sand habitats on Cape York Peninsula, Queensland. The new species is allied to D. petiolaris R.Br. ex DC. and D. lanata K.Kondo.
Corrections to the bryophyte names Porella cranfordi and Temnoma townrowii, and a note on Pyrrhobryum paramattense
Authors: Meagher David
Published: August 2020

Orthographic errors in the specific epithets of Porella cranfordi Steph. and Temnoma townrowii R.M.Schust. are corrected. The orthography of the specific epithet of Pyrrhobryum paramattense (Müll.Hal.) Manuel is discussed, and the original spelling is retained. The collector of the type of Pyrrhobryum paramattense was most likely Franz Wilhelm Sieber, not Charles von Hügel.
The Effectiveness of the Use of Aquatic Plants (Lemna perpusilla, Landoltia punctata and Azolla pinnata) in the Phytoremediation Process of Catfish Aquaculture Wastewater
Authors: Amyati . , Hasan Zahidah , Supriadi Dedi , Hamdani Herman
Published: August 2020

Aims: The purpose of this study was to determine aquatic plants (Lemna perpusilla, Landoltila punctata and Azolla pinnata) that have the most effective ability as phytoremediation agents for catfish cultivation wastewater.

Study Design: This research was conducted by an experimental method, with a Completely Randomized Design (CRD) consisting of three treatments and four replications.

Place and Duration of Study: This research is located at the Wet Laboratory (Ciparanje) of the Faculty of Fisheries and Marine Sciences, Padjadjaran University. Water quality testing is carried out at the Water Resources Laboratory of the Faculty of Fisheries and Marine Sciences. Research was carried out on 20 July-24 September 2019.

Methodology: The test wastewater was collected from catfish pond culture and put into twelve aquarium with a volume of 8 litre. Physical and chemical parameters observed include BOD5, dissolved oxygen, CO2 acidity, temperature, nitrate, and phosphate.

Results: Lemna perpusilla, Landoltia punctata and Azolla pinnata were able to improve the quality of catfish culture wastewater such as increasing the concentration of dissolved oxygen (DO) and pH, and reducingBOD5, CO2, nitrate and phosphate. Lemna perpusilla was able to reduce the concentration of BOD5, CO2,carbondioxide, nitrate and phosphate from catfish cultivation wastewater by75%; 77.7%; 23.4%; 44.2%, respectively, during the phytoremediation process, and Landoltia punctata was able to reduce the concentrations same parameters by 52%; 68.3%; 17.8%; 18.3% and Azolla pinnata by 41%; 84%; 15.3% and 28.4%.

Conclusion: Lemnaper pusillamay improve the quality of catfish culture wastewater better than Landoltia punctata and Azolla pinnata. Lemna perpusilla can be recommended as phytoremediation agents catfish cultivation wastewater to remediate organic matter before being discharged directly into water bodies.
Formulation of a Mathematical Model for the Transmission Dynamics of Infectious Bursal Disease (IBD), Incorporating Eects of Environmental Factors
Authors: Omollo Emily Atieno , Kimathi George
Published: August 2020

In this paper, we develop a four compartment model that explain the transmission dynamics of infectious bursal disease, considering the effects of environmental factors. Ordinary differential equations have been used in formulation of the model. Reproductive number (R0) has been derived using Next Generation Matrix. The disease free equilibrium is analyzed using Jacobian matrix and found to be locally and globally asymptotically stable when R0 < 1. We employ Routh-Hurwitz stability criterion to analyze the stability of endemic equilibrium. The numerical results indicates that contact with contaminated environment enhances the rate of transmission of the disease in the system.
Survey on Seed Sources and Quality Seed Availability in Telangana Districts
Authors: Prabhavathi Kona , Kanakadurga K. , Pradeep T. , Rao R. G. S.
Published: August 2020

Our study was conducted to understand the significance of existing seed systems and extent of seed availability of major crops viz., paddy, maize (cereals); red gram (pulses); and cotton (commercial crops) in 4 major agrarian districts (Mahbubnagar, Karimnagar, Warangal and Nalgonda) of Telangana state. There is a striking influence of seed source on the productivity & profitability of farmers, and hence, our study was aimed at understanding the nature and extent of seed quality parameters like genetic identity, genetic purity and seed health contributing to gross output of the crop. Our survey conducted during 2 Kharif & 2 Rabi seasons during 2017 to 2019 brought out interesting facts that formal sector contributes 96 to 100% of seed replacement rate (SRR) for commercial crops, 70 to 90% for cereals, 75 to 100% for pulses and negligible in case of oilseeds. The reasons for highest contribution of formal sector are due to prevalent seed subsidy schemes and also, availability of good quality seeds. The informal supply of seed majorly involves farmer to farmer exchange and farm saved seeds which is a major source of seeds to resource poor farmers.
tRNA: Structure and functions Report of a Pre‐Symposium held in Riga, U.S.S.R., on June 19 and 20, 1970, within the scope of the VII International Symposium on the Chemistry of Natural Products
Authors: Kisselev L. , Venkstern T.
Published: July 2002

The four sessions of the Pre‐symposium were devoted to four different aspects of the subject, these form the main divisions of the report. The Pre‐symposium was opened with an introductory speech by V.A.Engelhardt.
1H NMR study of long and short myosin S2 fragments
Authors: Stewart Murray , Roberts Gordon C.K.
Published: July 2002

The 270 MHz 1H NMR spectra of rabbit skeletal long and short S2 were indistinguishable at 20°C and 30°C and contained only a small proportion of sharp peaks associated with flexible regions. At 60°C both proteins were denatured and had essentially identical spectra. At 40°C and 50°C the long S2 spectrum contained a marginally greater proportion of sharp peaks, representing not more than 25 residues/chain. Our results are consistent with the presence of a small hinge in long S2 but do not support its containing an extensive region which provides contractile force by a helix—coil transition.
Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A
Authors: Matsuura Motohiro , Kojima Yasuhiko , Yuzuru Homma J. , Kubota Yoshiyuki , Yamamoto Akihiro , Kiso Makoto , Hasegawa Akira
Published: July 2002

Biological activities of five synthetic lipid A analogues (D‐glucosamine derivatives) were examined to elucidate the structure required for expression of the biological activities of endotoxin. Proclotting enzyme of horseshoe crab activation, interferon‐inducing and tumor necrosis factor‐inducing activities were significantly expressed by an analogue which possesses 4‐O‐phosphoryl, 3‐O‐tetradecanoyl and N‐tetradecanoyloxytetradecanoyl groups. The results obtained with different analogues show that the 4‐O‐phosphoryl and N‐tetradecanoyloxytetradecanoyl groups are important for expression of the above activities. The effect of 6‐O‐acylation in preventing the expression of these biological activities is also suggested. Pyrogenic activity was not detected in any of the compounds tested.
Chemical characterization of cyanogen bromide fragments from the β‐chain of human complement factor C3
Authors: Lundwall Åke , Hellman Ulf , Eggertsen Gösta , Sjöquist John
Published: July 2002

The isolated β‐chain of human complement factor C3 (C3β) was fragmented by cyanogen bromide. Nine fragments were defined by gel filtration and high‐pressure liquid chromatogaphy, and characterized with respect to their M
r, amino acid composition and N‐terminal amino acid sequence. Approx. 30% of the primary structure of C3β was determined. Alignment of the 3 N‐terminal fragments allowed determination of 61 of the amino terminal residues of C3β. This region demonstrated 40% homology with the sequence in the N‐terminal segment of the α‐chain of the cobra venom factor.
Amino acid sequence of the N‐terminal region of human hemopexin
Authors: Frantíková Věra , Borvák Josef , Kluh Ivan , Morávek Ladislav
Published: July 2002

Cyanogen bromide digestion of hemopexin at its 6 methionine residues results in 7 fragments (CB1–CB7) partially connected by disulfide bridges. By sequence studies of fragments CB1‐CB4 and peptides prepared by their enzyme cleavage, a continuous amino acid sequence of the N‐terminal region of human hemopexin, comprising 220 amino acid residues, was determined. The presence of intramolecular disulfide bonds, connecting half‐cystine residues and , was proved in fragments CB2 and CB3. Fragments CB1–CB4 include 5 sites, where hexosamine oligosaccharides are attached (positions 1,41,164, 217 and probably 223). In the sequenced region two sites sensitive to acid hydrolysis ‐ bonds ⋯ Asp‐Pro ⋯ in positions and were found. In spite of the fact that pooled material of many donors was studied, no sequence heterogeneity was discovered.
Phosphorus‐31 nuclear magnetic resonance studies of photosynthesizing Chlorella
Authors: Mitsumori Fumiyuki , Ito Osamu
Published: July 2002

31P‐NMR Chlorella Intracellular pH Chloroplast Cytoplasm Photophosphorylation
tRNA binding to programmed ribosomes increases the ribosomal affinity for tuberactinomycin O
Authors: Yamada Takeshi , Teshima Tadashi , Shiba Tetsuo , Nierhaus Knud H.
Published: July 2002

The binding of 14C‐labelled tuberactinomycin O was analysed in equilibrium dialysis cells. The ionic conditions and the concentration of the labelled drug used in the binding assays allowed the binding of just one drug molecule per non‐programmed ribosome. Under these conditions, the occupation of the ribosomal P‐site by deacylated tRNAPhe in the presence of poly(U) increased the amount of [14C]tuberactinomycin O bound by a factor of two. Kanamycin, gentamicin and neomycin reduced the binding of tuberactinomycin O, whereas chloramphenicol, tetracycline, streptomycin and puromycin had no effect. A stimulation of the binding of tuberactinomycin O was found upon addition of erythromycin.
Photo CIDNP study on the complex formation of λ‐ cro protein with OR3
Authors: Shirakawa M. , Lee S.J. , Akutsu H. , Kyogoku Y. , Kitano K. , Shin M. , Ohtsuka E. , Ikehara M.
Published: July 2002

A photo CIDNP spectrum of λ cro repressor protein showed that one of the three tyrosines and His 35 are quite accessible to the photosensitive dye. For the remaining two tyrosine residues one is slightly accessible, but the other is inaccessible. In comparison with the result of differential nitration at tyrosine side chains followed by the peptide analysis, it can be concluded that Tyr 26 is mostly exposed and Tyr 51 is slightly exposed on the surface of the cro dimer. On the addition of OR3 17mer, His 35 and Tyr 26 are no longer accessible to the dye, which indicates that they are involved in interaction. However, a similar phenomenon was observed by adding CAP binding site 22mer. The interaction mechanism will be discussed.
Factors affecting polyamine excretion from mammalian cells in culture
Authors: Wallace Heather M. , Keir Hamish M.
Published: July 2002

Canavanine, diaminopropane, α‐methylornithine and methylglyoxal bis(guanylhydrazone) decreased the intracellular polyamine concentrations in growing baby hamster kidney cells. Each of the inhibitors also prevented polyamine efflux into the extracellular medium. Concomitant with the decrease in polyamine excretion was a change in the distribution of polyamines in the extracellular medium. In each case there was a decrease in the amount of radioactivity present as free spermidine and an increase in that found as acetyl polyamines. The magnitude of this shift correlated with the degree of inhibition of excretion. It may be that acetyl polyamines play a role in the regulation of polyamine excretion.
Acquisition of thermotolerance in Saccharomyces cerevisiae without heat shock protein hsp104 and in the absence of protein synthesis
Authors: De Virgilio Claudio , Piper Peter , Boller Thomas , Wiemken Andres
Published: July 2002

Acquisiton of thermotolerance in response to a preconditioning heat treatment at 40°C was studied in mutants of the yeast Saccharomyces cerevisiae lacking a specific heat shock protein or the ability to synthesize proteins at 40°C. A mutant carrying a deletion or heat shock protein hsp104 and the corresponding wildtype strain were both highly sensitive to heat stress at 50.4°C without preconditioning but both acquired almost the same level of thermotolerance after 60 min of preconditioning. Both strains showed equal induction of trehalose‐6‐phosphate synthase and accumulated equal levels of trehalose during the treatment. The conditional mutant ts ‐ 187 synthesized no proteins during the preconditioning heat treatment but nevertheless acquired thermotolerance, albeit to a lesser degree than the corresponding wildtype strain. Induction of trehalose‐6‐phosphate synthase and accumulation of trehalose were reduced to a similar extent. These results show that acquisition of thermotolerance and accumulation of trehalose are closely correlated during heat preconditioning and are modulated by protein synthesis but do not require it.
Families of metalloendopeptidases and their relationships
Authors: Jiang Weiping , Bond Judith S.
Published: July 2002

Crystal structures available for four metalloendopeptidases have revealed zinc ligands for these enzymes. New sequence information has made it possible to compare the primary structures of the zinc‐binding site in metalloendopeptidases. A scheme based on the zinc‐binding site is proposed to classify metalloendopeptidases into five distinct families: thermolysin, astacin, serratia, matrixin, and snake venom metalloproteinases. Two histidines and one glutamate are zinc‐ligands in the thermolysin family. Three histidines and one tyrosine are zinc ligands in other four families, which are further distinguished by the identity of the residue following the third histidine and by the environment surrounding the tyrosine.
Infrared studies of octopus rhodopsin
Authors: Masuda Satoshi , Monta Eugene H. , Tasumi Mitsuo , Iwasa Tatsuo , Tsuda Motoyuki
Published: July 2002

The infrared absorption spectra of octopus rhodopsin and its photoproducts have been observed at 282K and 210K under irradiation of blue and orange light in a neutral condition. The acid metarhodopsin‐minus‐rhodopsin and lumirhodopsin‐minus‐rhodopsin difference spectra have been obtained. A new intermediate (called transient acid metarhodopsin) with a lifetime of about 5 s has been found to exist prior to acid metarhodopsin. The present results, together with the data obtained previously, give information on the state of the carboxylic group in the side chain of Asp‐81, which is the only acidic amino‐acid residue in the part of opsin buried inside the membrane. This carboxylic group is protonated throughout the transformation series, but its state changes on going from transient acid metarhodopsin to acid metarhodopsin. It is probable that these two photoproducts are different from each other only in the opsin moiety.
Action of nitric oxide as an antioxidant against oxidation of soybean phosphatidylcholine liposomal membranes
Authors: Hayashi Katsunobu , Noguchi Noriko , Niki Etsuo
Published: July 2002

To elucidate the protective role of nitric oxide (NO) against lipid peroxidation, the effect of NO donor on the formation of lipid hydroperoxide and consumption of α‐tocopherol in the oxidation of soybean phosphatidylcholine liposomal membranes was studied. The oxidation was induced by either aqueous or lipophilic peroxyl radicals generated by the hydrophilic or lipophilic azo compound, respectively. It was found that NO acted as a potent antioxidant by scavenging peroxyl radicals rapidly. It was also found that NO was capable of penetrating multilamellar membranes to scavenge lipid peroxyl radicals and spare α‐tocopherol.
Zopiclone in the treatment of insomnia in depressed patients
Authors: Van Moffaert M , Pilate C
Published: July 2002

During the early treatment of a major depressive episode with amitryptiline, insomnia was treated in 81 patients in a double-blind comparative trial comparing zopiclone and flunitrazepam. The study showed no major differences in the efficacy profile and showed better tolerability for zopiclone than for flunitrazepam.
ERK activation upon hypoxia: involvement in HIF‐1 activation
Authors: Minet E , Arnould T , Michel G , Roland I , Mottet D , Raes M , Remacle J , Michiels C
Published: July 2002

Hypoxia‐inducible factor‐1 (HIF‐1) is a transcription factor activated by hypoxia. The HIF‐1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kinases (ERK) in hypoxia and their involvement in HIF‐1 activation. We demonstrated that in human microvascular endothelial cells‐1 (HMEC‐1), ERK kinases are activated during hypoxia. Using dominant negative mutants, we showed that ERK1 is needed for hypoxia‐induced HIF‐1 transactivation activity. Moreover, using a kinase assay and Western blot experiments, we showed that HIF‐1α is phosphorylated in hypoxia by an ERK‐dependent pathway. These results evidence the role of mitogen‐activated protein kinase in the transcriptional response to hypoxia.
Characterization of Solt, a novel SoxLZ/Sox6 binding protein expressed in adult mouse testis
Authors: Yamashita Atsushi , Ito Michihiko , Takamatsu Nobuhiko , Shiba Tadayoshi
Published: July 2002

SoxLZ/Sox6, a member of the Sox protein family, contains a leucine zipper motif in addition to an HMG box, which is its DNA binding domain. Here we have identified a novel SoxLZ/Sox6 binding protein, termed Solt, which we obtained independently using both a far‐Western blot and a yeast two‐hybrid screen. Like SoxLZ/Sox6 mRNA, Solt mRNA was exclusively expressed in the testis in mouse. Solt contains an unusual leucine zipper, which bound to the leucine zipper region of SoxLZ/Sox6 in vitro. In transient transfection assays in CHO cells with SoxLZ/Sox6 containing the transactivational region of herpes simplex virus VP16, expression of a reporter gene that carries a cis binding region for Sox proteins was significantly enhanced by the co‐expression of Solt and Ca2+/calmodulin‐dependent protein kinase IV.
Functional role of the HIV‐1 Rev exon 1 encoded region in complex formation and trans‐dominant inhibition
Authors: Gjerdrum Christine , Stranda Annicke , Szilvay Anne Marie
Published: July 2002

To study functional aspects of the exon 1 encoded region of the human immunodeficiency virus type 1 Rev protein, the viral Tev protein which exhibits low Rev activity but lacks the rev exon 1 encoded region was examined. Neither Rev–Tev heteromer complex formation nor inhibition of Rev by an export deficient Tev mutant was observed. Insertion of the rev exon 1 encoded region into the Tev mutant allowed it to oligomerize with Rev and act as a trans‐dominant negative mutant. This showed that the exon 1 encoded region of Rev is essential for oligomerization and that oligomerization is a prerequisite for trans‐dominant inhibition.
The propeptide of subtilisin BPN′ as a temporary inhibitor and effect of an amino acid replacement on its inhibitory activity
Authors: Kojima Shuichi , Minagawa Tetsuya , Miura Kin-ichiro
Published: July 2002

The propeptide of subtilisin‐family proteases is known to exhibit inhibitory activity toward a cognate protease in addition to its function as an intramolecular chaperone. For detailed investigation of its inhibitory properties, the propeptide of subtilisin BPN′ was produced in Escherichia coli. Inhibitory activity measurements and electrophoresis showed that the propeptide was a temporary inhibitor, which was initially potent but was gradually degraded by subtilisin BPN′ through specific intermediates. The main cleavage site was identified as Glu53–Lys54, with minor sites at Thr17–Met18 and Met21–Ser22, which were located in turn regions of the propeptide in the complex with subtilisin BPN′. Since the isolated propeptide has been shown not to form a tertiary structure, these results indicate that main digestions proceed through proteolytic attack of subtilisin toward the accessible sites of the propeptide in the complex with subtilisin. Therefore, replacement of Glu53 at the main cleavage site by Asp, which is a less favorable amino acid than Glu for subtilisin, makes the propeptide a more resistant temporary inhibitor.
Cloning and characterization of a Drosophila adenylyl cyclase homologous to mammalian type IX
Authors: Iourgenko Vadim , Kliot Benjamin , Cann Martin J. , Levin Lonny R.
Published: July 2002

A novel Drosophila adenylyl cyclase (AC) was identified by PCR using degenerate primers specific for the known metazoan ACs. The full‐length cDNA predicts a protein displaying significant sequence homology with mammalian Type IX AC (AC9). The abundance and size of the message for the Drosophila AC9 homolog (DAC9) changes through development. Biochemical analysis of DAC9 confirms it encodes a functional enzyme which can be activated by forskolin or G protein. Together with the Drosophila Type I AC homolog encoded by the learning and memory gene, rutabaga, the molecular identification of DAC9 demonstrates there is a family of Drosophila AC isoforms reflecting at least part of the diversity of mammalian AC isoforms.
Non‐oxidative modification of low density lipoprotein by ruptured myocytes
Authors: Bourne Louise C , Lamb David J , Collis Cliff S , O'Brien Michael , Leake David S , Rice-Evans Catherine
Published: July 2002

In this study, the interaction of ruptured cardiac myocytes with low density lipoprotein (LDL) has been investigated and the consequent extent of uptake by macrophages. The results show that lysate released from ruptured myocytes is capable of inducing LDL oxidation and that the resulting modified form is recognised and degraded by macrophages. Peroxyl radical scavengers inhibit the LDL oxidation but not the macrophage uptake suggesting that LDL can be modified by mechanisms that are independent of oxidative processes by intracellular constituents of cardiac myocytes.
Expression of messenger RNA for the prostaglandin D receptor in the leptomeninges of the mouse brain
Authors: Oida Hiroji , Hirata Masakazu , Sugimoto Yukihiko , Ushikubi Fumitaka , Ohishi Hitoshi , Mizuno Noboru , Ichikawa Atsushi , Narumiya Shuh
Published: July 2002

The localization of prostaglandin D receptor in the mouse brain was examined by in situ hybridization histochemistry. The autoradiography showed significant hybridization signals of mRNA for prostaglandin D receptor in the leptomeninges covering the surface of the brain, but not in neurons or glia in the brain parenchyma. This finding was confirmed by Northern blot analysis using mRNA prepared from either the whole brain with the leptomeninges, brain parenchyma without the leptomeninges or the leptomeninges alone. A weak signal corresponding to the major 3.5‐kbp transcript was detected in the whole brain. This band was significantly enriched in the leptomeninges, but was not detected in the brain parenchyma. These results suggest that prostaglandin D receptor is most highly, if not exclusively, expressed in the leptomeninges of the mouse brain.
Structural organization of the bovine cathelicidin gene family and identification of a novel member1
Authors: Scocchi Marco , Wang Shenglun , Zanetti Margherita
Published: July 2002

Cathelicidins are a group of myeloid antimicrobial peptide precursors found in a variety of mammalian species. Transcripts of this family show a highly conserved 5′ region corresponding to the 5′ untranslated region, signal peptide and propiece, and diverse 3′ regions encoding structurally varied C‐terminal sequences that correspond to mature antimicrobial peptides after proteolytic release from the precursors. To establish the size of the bovine gene family encoding these proteins, λ genomic clones were isolated by screening a bovine library with a probe based on the conserved cDNA region of bovine members. Restriction mapping, hybridization studies and sequence analysis identified 11 distinct genes that based on the intergenic distances of contiguous genes appear to be in close physical proximity. Among these, a novel gene encoding the precursor of a putative α‐helical antimicrobial peptide was recognized and sequenced. The novel gene appears to be expressed in bovine bone marrow myeloid cells, spleen and testis.
RanBP1 is crucial for the release of RanGTP from importin β‐related nuclear transport factors
Authors: Bischoff F.Ralf , Görlich Dirk
Published: July 2002

Nucleocytoplasmic transport appears mediated by shuttling transport receptors that bind RanGTP as a means to regulate interactions with their cargoes. The receptor·RanGTP complexes are kinetically very stable with nucleotide exchange and GTP hydrolysis being blocked, predicting that a specific disassembly mechanism exists. Here we show in three cases receptor·RanGTP·RanBP1 complexes to be the key disassembly intermediates, where RanBP1 stimulates the off‐rate at the receptor/RanGTP interface by more than two orders of magnitude. The transiently released RanGTP·RanBP1 complex is then induced by RanGAP to hydrolyse GTP, preventing the receptor to rebind RanGTP. The efficient release of importin β from RanGTP requires importin α, in addition to RanBP1.
Caspase 7‐induced cleavage of kinectin in apoptotic cells
Authors: Machleidt Thomas , Geller Patricia , Schwandner Ralf , Scherer Gudrun , Krönke Martin
Published: July 2002

Kinectin has been characterized as the first known receptor for the molecular motor kinesin, which is critically involved in microtubule‐based vesicle transport and membrane trafficking. Here we identify kinectin as a target for caspase‐mediated proteolysis during apoptosis. Treatment of cells with diverse apoptotic stimuli including TNF, anti‐Fas, anticancer drugs, γ‐radiation or ceramide leads to rapid proteolytic cleavage of the 160‐kDa form of kinectin to a 120‐kDa fragment. Evidence is provided that kinectin cleavage is mediated by caspase 7.
Expression and characterization of human PDEδ and its Caenorhabditiselegans ortholog CEδ
Authors: Li Ning , Baehr Wolfgang
Published: July 2002

Cyclic GMP phosphodiesterase (PDE) is rod photoreceptor disk membrane‐associated via C‐terminal lipid tails. PDEδ, a recently identified subunit, was shown to disrupt PDE/membrane interaction under physiological conditions, without affecting PDE catalytic activity. We found that a PDEδ ortholog from the eyeless nematode Caenorhabditis elegans (termed CEδ) solubilizes bovine PDE in vitro with an EC50 very similar to PDEδ. Immobilized PDEδ and CEδ both bind, in addition to bovine PDE, an N‐terminal fragment of human retinitis pigmentosa GTPase regulator, but not rhodopsin kinase and Ran binding protein 1. The results suggest that PDEδ and CEδ may regulate membrane binding of a variety of proteins in photoreceptors and other tissues.
Involvement of a chloroplast homologue of the signal recognition particle receptor protein, FtsY, in protein targeting to thylakoids
Authors: Kogata Naoko , Nishio Kazuaki , Hirohashi Toshiya , Kikuchi Shingo , Nakai Masato
Published: July 2002

We isolated an Arabidopsis thaliana cDNA whose translated product shows sequence similarity to the FtsY, a bacterial homologue of SRP receptor protein. The Arabidopsis FtsY homologue contains a typical chloroplast transit peptide. The in vitro‐synthesized 37 kDa FtsY homologue was imported into chloroplasts, and the processed 32 kDa polypeptide bound peripherally on the outer surface of thylakoids. Antibodies raised against the FtsY homologue also reacted with a thylakoid‐bound 32 kDa protein. The antibodies inhibited the cpSRP‐dependent insertion of the light‐harvesting chlorophyll a/b‐binding protein into thylakoid membranes suggesting that the chloroplast FtsY homologue is involved in the cpSRP‐dependent protein targeting to the thylakoid membranes.
PiUS (Pi uptake stimulator) is an inositol hexakisphosphate kinase
Authors: Schell Michael J. , Letcher Andrew J. , Brearley Charles A. , Biber Jürg , Murer Heini , Irvine Robin F.
Published: July 2002

A cDNA cloned from its ability to stimulate inorganic phosphate uptake in Xenopus oocytes (phosphate uptake stimulator (PiUS)) shows significant similarity with inositol 1,4,5‐trisphosphate 3‐kinase. However, the expressed PiUS protein showed no detectable activity against inositol 1,4,5‐trisphosphate, nor the 1,3,4,5‐ or 3,4,5,6‐isomers of inositol tetrakisphosphate, whereas it was very active in converting inositol hexakisphosphate (InsP6) to inositol heptakisphosphate (InsP7). PiUS is a member of a family of enzymes found in many eukaryotes and we discuss the implications of this for the functions of InsP7 and for the evolution of inositol phosphate kinases.
Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders
Authors: Vigil‐De Gracia P.
Published: July 2002

Objective: to report the experience clinical, biochemical findings, complications and the maternal–perinatal outcome in patients with HELLP syndrome and acute fatty liver of pregnancy (AFLP) during the same period. Materials and methods: during the period between January 1996 and December 1999, medical records of patients with the discharge diagnosis of AFLP and HELLP syndrome were reviewed for presenting symptoms, laboratory findings, maternal and perinatal complications. Routine laboratory evaluation included serial measurement of liver function tests, complete blood cell count, coagulation profile and renal function tests. Results: during the study period 10 patients had AFLP and 75 women had HELLP syndrome as the discharge diagnosis. Patients with HELLP syndrome had major parity than AFLP (P<0.006). The most common presenting symptom for patients with AFLP was malaise noted in all patients, nausea and/or vomiting, abdominal pain and jaundice were very common. Headache, abdominal or epigastric pain and hematuria were the most common symptoms of patients with HELLP syndrome. Women with AFLP had major hypoglycemia, hypocholesterolemia, hypotriglyceridemia, serum transaminase activity and low antithrombin III. Disseminated intravascular coagulation, acute renal insufficiency, ascites, seroma and encephalophaty were more common with AFLP. Conclusions: our opinion is that AFLP had clinical presentation, biochemical findings and complications clearly distinguished of HELLP syndrome.
Techniques for improving response rates in OM survey research
Authors: Frohlich Markham T
Published: July 2002

Response rates are an important indicator of survey research success and a methodological concern in OM today. An analysis was done of 233 OM survey research papers published over the past 12 years which showed that the average managerial response rate flattened‐out in the mid‐1990s at, approximately 32% and has not improved since then. This paper goes on to examine the theories and techniques found in the diverse survey research literature on improving response rates including OM survey research benchmarks that achieved very high response rates. By following the tactics outlined in this paper, OM survey researchers stand an excellent chance of not only improving the overall respondent yields for their studies but also reducing the bias caused by non‐response.
Analysis of cerebrocortical neuronal migration in three‐dimensional fetal mouse cerebral explants: comparison with in vivo
Authors: Humphreys Peter , Hendelman Walter
Published: July 2002

Organotypic cultures of cerebral mantle offer a useful method for in vitro investigation of mechanisms involved in the migration of neuronal precursors to the neocortex. Studies reported to‐date have indicated that, while neurons continue to migrate in cerebral explant cultures for a few days, they eventually stop migrating and fail to reach their pre‐programmed destinations and thus distinct layers fail to develop within the cortical plate. Hypothesizing that this migrational arrest stemmed, in part, from severe distortion and flattening of explants in the roller‐tube culture method used in previous studies by others, we studied neocortical neuronal migration using a recently developed three‐dimensional explant culture system. Explants 300–350 μm thick were derived from E16 fetal mouse cerebrum 24 h following administration of 5‐bromodeoxyuridine (BrdU), encased in collagen, placed on porous membranes, and alternately exposed to medium and air on a rocking platform. Cultures were maintained for 7, 11 and 14 days, then analyzed for the location of BrdU‐labeled cells. Newborn mice labeled at E15 and analyzed at P1 and P9 served as controls. In the explants, labeled cells continued to migrate into the cortical plate until 11 days in culture, at which point the ventricular zone had disappeared and two distinct cortical cell layers sometimes developed. BrdU‐labeled cells were present throughout the cortical plate, particularly the mid portion. In P9 controls, five distinct cortical layers were present with labeled cells mostly in the outer half (layers II, III). Thus, preservation of three‐dimensional tissue integrity in culture was accompanied by a modest improvement in migration of neurons to the neocortex in comparison with previous reports. The fact that normal layer formation failed to develop in thick explants suggests that factors other than tissue distortion contribute to this outcome.
Viktor Hamburger's Department of Zoology in the 1940s: a student perspective
Authors: Wenger Byron S. , Wenger Eleanor
Published: July 2002

Eleanor and Byron Wenger were graduate students in the Department of Zoology in the 1940s. Both took several courses with Viktor, and he was thesis advisor for both of us. We have attempted to provide a summary of life in the department from a student perspective as well as our impression of Viktor's style of mentoring and guiding student research and education.
Developmentally induced microencephalopathy in guinea pigs ‐embryonic glial cell activation marks selective neuronal death
Authors: Roßner Steffen , Brückner Martina K. , Bigl Volker
Published: July 2002

We have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) on gestation day (GD) 24 results in neocortical microencephalopathy, increased protein kinase C activity and altered processing of the amyloid precursor protein in neocortex of the offsprings. In order to identify the primary neuronal lesions produced by MAM‐treatment, we mapped the 5‐bromo‐2’‐deoxyuridine (BrdU)‐incorporation in dividing neurons on GD 24 and we followed the effects of MAM‐treatment on GD 24 on embryonic immediate early gene expression and on glial cell activation. BrdU injected on GD 24 labeled many neurons of the ventricular zone and of the intermediate zone but only scattered neurons of the cortical plate. When time‐mated guinea pigs were injected intraperitoneally with MAM on GD 24, we observed the activation of microglial cells in the ventricular/intermediate zone and the appearence of astrocytes between the intermediate zone and the cortical plate, 48 h after intoxification. The activation of glial cells was accompanied by the neuronal expression of c‐Fos but not of c‐Jun in the ventricular/intermediate zone. Based on our observations on BrdU‐incorporation and on the morphological outcome of MAM treatment in the juvenile guinea pig, our data presented here indicate that selective neurodegeneration during development induces the activation of both phagocytotic microglial cells and of astrocytes which might trophically support damaged neurons surviving this lesion procedure.
Evidence that the loss of Purkinje cells and deep cerebellar nuclei neurons in homozygous weaver is not related to neurogenetic patterns
Authors: Martı́ Joaquı́n , Wills Katherine V. , Ghetti Bernardino , Bayer Shirley A.
Published: July 2002

To determine whether the neurogenetic patterns of Purkinje cells and deep cerebellar nuclei neurons were normal in weaver homozygotes and whether the degeneration of those neuronal types was linked to their time of origin, [3H] thymidine autoradiography was applied on sections of homozygous weaver mice and normal controls on postnatal day 90. The experimental animals were the offspring of pregnant dams injected with [3H] thymidine on embryonic days 11–12, 12–13, 13–14 and 14–15. The results show that the onset of neurogenesis, its pattern of peaks and valleys, and its total span were similar between wild type and homozygous weaver in the cerebellar areas analyzed, indicating that the loss of Purkinje cells and deep cerebellar nuclei neurons is not related to neurogenetic patterns. In weaver homozygotes, the loss of Purkinje cells and deep cerebellar nuclei neurons followed a lateral to medial gradient of increasing severity. Thus, the vermis and the fastigial nucleus, which are medially located, presented the most important neuron loss, whereas in the lateral hemisphere and the dentate nucleus, neuron loss was spared.
Behaviour of gliomas in vitro vs histopathological grading
Authors: de Ridder L.
Published: July 2002

Infiltration of primary cultured human gliomas into host tissue in vitro is correlated to the histological grade of tumours they are derived from. The higher the malignancy grade, following the WHO classification, the higher the number of tumours expressing an infiltrative pattern in vitro. To select the putative infiltrative cells from freshly collected brain tumour material, tumour fragments are explanted in vitro and primary monolayers are grown. From these cultures flaps of viable and proliferating tumour‐derived cells are placed in contact with embryonic host tissue forming a confrontation culture. If infiltrative cells are present in the monolayer, they will infiltrate into the host tissue and replace it in a progressive way: they express an infiltrative pattern. If no infiltrative cells are present, host and tumour‐derived cells will stay together expressing a noninfiltrative pattern.

So analysis of the confrontation pattern in vitro observed for individual gliomas, collected by a stereotactic biopsy, might help the neurosurgeon to set up a surgical strategy.
The NG2 chondoitin sulfate proteoglycan: role in malignant progression of human brain tumours
Authors: Chekenya M. , Rooprai H.K. , Davies D. , Levine J.M. , Butt A.M. , Pilkington G.J.
Published: July 2002

The expression and function of NG2, a transmembrane chondroitin sulfate proteoglycan was studied in human gliomas of various histological types in culture using immunocytochemistry and flow cytometry. NG2 was differentially expressed in the neoplasms, with higher expression in high compared to low‐grade gliomas. In acutely isolated cells from human biopsies, NG2 +ve and NG2 −ve populations were morphologically distinct from each other, and NG2 +ve cells were more proliferative than NG2 −ve cells. The mitogens platelet derived growth factor (PDGF‐AA) and basic fibroblast growth factor (bFGF) added in combination to serum‐free medium (SFM) upregulated NG2 expression on glioblastoma multiforme cells in culture but had little effect on NG2 expression on the anaplastic astrocytoma cells. Furthermore, NG2 was colocalised with the platelet derived growth factor alpha receptor (PDGFαR) and antibody blockade of the PDGF‐αR ablated NG2 expression on the glioblastoma multiforme cells, suggesting that increased NG2 expression in the presence of PDGF‐AA is mediated via the PDGF‐αR. Assays of migration and invasion indicate that NG2 +ve glioma cells migrated more efficiently on collagen IV and that NG2 −ve cells were more invasive than their NG2 +ve counterparts. The results indicate that NG2 may be, respectively, positively and negatively related to the proliferative and invasive capacity of glioma cells. Thus, expression of the NG2 proteoglycan may have major implications for malignant progression in glial neoplasms and may prove a useful target for future therapeutic regimens.
Comparison of the cost-effectiveness of milnacipran (a SNRI) with TCAs and SSRIs: a modeling approach
Authors: Dardennes R , Berdeaux G , Lafuma A , Fagnani F
Published: July 2002

A simulation model based on the theory of clinical decision analysis was used to compare outcomes and costs when treating patients with major depressive episodes using either a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA), in comparison with milnacipran (a serotonin), and a norepinephrine re-uptake inhibitor (SNRI). The clinical data used were taken from published meta-analyses. This analysis supports: (1) a comparable efficacy of milnacipran and TCA with a better tolerance; and, (2) an advantage of milnacipran over SSRI for efficacy with a comparable tolerance. Based on these findings, a decision tree was constructed with the assistance of a panel of psychiatrists in order to provide a model of usual clinical practice. Estimates not available from clinical studies were obtained either from literature analysis or from the panel.

Economic appraisal was performed according to the viewpoint of the French national sickness fund (sécurité sociale), and expenditure assessment was limited to direct costs (hospitalizations, antidepressant medications, visits, and laboratory tests). The results suggest that milnacipran is a cost-effective alternative: the expected cost of treatment per depressive episode is lower than either a French representative panel of TCAs (a saving of 288 FF), or SSRIs (a savings of 961 FF). The expected length of clinical remission is slightly higher than comparators. The robustness of these findings was supported by sensitivity analyses.