bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced external quantum efficiency of light emitting diodes by fabricating two-dimensional photonic crystal sapphire substrate with holographic technique
Authors: Lin Han  , Liu Shou  , Zhang Xiang-Su  , Liu Bao-Lin  , Ren Xue-Chang  ,   厦门大学物理系，厦门  361005
Published: December 2020

Investigation in fabricating two-dimensional (2D) photonic crystal (PC) on sapphire substrates for enhancing external efficiency of GaN based light emitting diodes (LEDs) is presented. 2D-PC was fabricated on a sapphire substrate using holographic lithography and inductively coupled plasma (ICP) dry etching. LEDs with 2μm thick n-GaN layer，four pairs of InGaN/GaN quantum well structures and 200nm thick p-GaN layer were grown on the patterned sapphire substrate (PSS) by metal organic chemical vapor deposition (MOCVD). The PC fabricated on PSS has 2D hexagonal lattice pattern，with 3.8μm lattice constant and 800nm depth. LED output measurement shows 100% increase in the average luminous intensity of PSS-LEDs compared with that of conventioanl LEDs. The measured X-ray rocking curves of (0002) diffraction for GaN layers grown on patterned and non-patterned sapphire substrates indicate that the quality of GaN crystal grown on PSS is not improved，which implies that the large enhancement of external quantum efficiency of PSS-LED is not caused by the increase in internal efficiency but possibly by the increase in extraction efficiency，which results from the scattering of the PSS.
Postoperative Outcomes for Plate-Screw Fixation in Adolescent Patients with Ankle Fracture
Authors: Talmaç Mehmet Ali , Görgel Mehmet Akif , Yahşi Yusuf , Kanar Muharrem , Seker Ali , Özdemir Haci Mustafa
Published: December 2020

Backround

We compared postoperative outcomes in adolescent patients who did and did not undergo plate-screw fixation of at least one of the lateral, medial, or posterior malleoli in ankle fractures. It was hypothesized that using plate-screw fixation would not negatively affect postoperative outcomes.

Methods

All of the preoperative data and postoperative outcomes for 56 patients with ankle fractures aged 12 to 15 years who underwent surgical treatment between January 1, 2007, and December 31, 2017, were reviewed retrospectively. Patients were grouped into plate-screw fixation (n = 15) and non–plate-screw fixation (n = 41) groups and as high- and low-energy trauma patients.

Results

There were no significant differences in postoperative outcomes between the plate-screw fixation and non–plate-screw fixation groups. The mean American Orthopaedic Foot & Ankle Society score of high-energy trauma patients was significantly lower than that of low-energy trauma patients (P < .001), and the rate of degenerative change in high-energy trauma patients was significantly higher than that in low-energy trauma patients (P = .008). There were no significant differences between high- and low-energy trauma patients with respect to other postoperative outcomes.

Conclusions

If anatomical reduction is performed without damaging the growth plate, postoperative clinical outcomes may be near perfect regardless of screw-plate fixation use. Postoperative outcomes of adolescent ankle fracture after high-energy trauma, independent of Salter-Harris classification and surgical treatment methods, were negative.
Determinants of behavioural and biological risk factors for cardiovascular diseases from state level STEPS survey (2017–19) in Madhya Pradesh
Authors: Kokane Arun M. , Joshi Rajnish , Kotnis Ashwin , Chatterjee Anirban , Yadav Kriti , Revadi G , Joshi Ankur , Pakhare Abhijit P.
Published: December 2020

Background

National and statewide assessment of cardiovascular risk factors needs to be conducted periodically in order to inform public health policy and prioritise allocation of funds, especially in LMICs. Although there have been studies from India which have explored the determinants of cardiovascular risk factors, they have mostly been from high epidemiological transition states. The present study assessed the determinants of cardiovascular (CVD) risk factors in a low epidemiological transition state (Madhya Pradesh) using the WHO STEPwise approach to surveillance (STEPS).

Methods

A total of 5,680 persons aged 18–69 years were selected from the state of Madhya Pradesh through multi-stage cluster random sampling. Key CVD risk factors we sought to evaluate were from behavioural (tobacco, alcohol, physical activity, diet) and biological domains (overweight or obese, Hypertension, Diabetes, and Raised serum cholesterol). Key socio-demographic factors of interest were the caste and tribe groups, and rural vs urban location, in addition to known influencers of CVD risk such as age, gender and education level

Results

Those belonging to the scheduled tribes were more at risk of consuming tobacco (OR 2.13 (95% CI [1.52–2.98]), and a diet with less than five servings of fruits and vegetables (OR 2.78 (95% CI [1.06–7.24]), but had had the least risk of physical inactivity (OR 0.31 (95% CI [0.02–0.54]). Residence in a rural area also reduced the odds of physical inactivity (OR 0.65 (95% CI [0.46–0.92])). Lack of formal education was a risk factor for both tobacco consumption and alcohol intake (OR 1.40 (95% CI [1.08–1.82]) for tobacco use; 1.68 (95% CI [1.14–2.49]) for alcohol intake). Those belonging to schedules tribes had much lower risk of being obese (OR 0.25; 95% CI [0.17–0.37]), but were at similar risk of all other clinical CVD risk factors as compared to other caste groups.

Conclusion

In the current study we explored socio-demographic determinants of behavioural and biological CVD risks, and found that in Madhya Pradesh, belonging to a scheduled tribe or living in a rural location, protects against being physically inactive or being overweight or obese. Increasing age confers a greater CVD-risk in all domains. Being a male, and lack of formal education confers a greater risk for behavioural domains, but not for most clinical risk domains. Future efforts at curbing CVDs should be therefore two pronged –a population-based strategy targeting biological risk factors, and a more focussed approach directed at those displaying risky behaviour.
Characterization of cytochrome b in the isolated ubiquinol‐cytochrome c2 oxidoreductase from Rhodopseudomonas sphaeroides GA
Authors: Gabellini Nadia , Hauska Günter
Published: July 2002

Extinction coefficients for cytochrome b and c
1 in the isolated cytochrome bc
1 complex from Rhodopseudomonas sphaeroides GA have been determined. They are 25 mM−1.cm−1 at 561 nm for cytochrome b and 17.4 mM−1.cm−1 at 553 nM for cytochrome c
1 for the difference between the reduced and the oxidized state. Cytochrome b is present in two forms in the complex. One form has an E
m7 of 50 mV, an α‐peak of 557 nm at liquid N2 temperature and of 561 nm at RT, which is red‐shifted by antimycin A. The other form has an E
m7 of −90 mV, a double α‐peak of 555 and 561 nm at liquid N2 temperature corresponding to 559 and 566 nm at RT. The absorption at 566 nm is red‐shifted by myxothiazol. The two shifts are independent of each other. Both midpoint potentials of cytochromes b are pH‐dependent. The redox center compositions of the cytochrome bc
1 complexes from Rhodopseudomonas sphaeroides and from mitochondria are identical.
Adenylate cyclase and guanylate cyclase in the excitable ciliary membrane from Paramecium: Separation and regulation
Authors: Klumpp Susanne , Gierlich Doris , Schultz Joachim E.
Published: July 2002

Particulate adenylate cyclase (AC) and guanylate cyclase (GC) activities localized in the ciliary membrane from Paramecium were solubilized by a two‐step procedure using the detergents Brij 56 and Lubrol PX. The enzymes remained in the supernatant after a 100 000 × g centrifugation. Upon gel chromatography, AC and GC were almost completely separated proving that each enzyme is a distinct molecular entity. Solubilization of GC was achieved with the calmodulin subunit remaining firmly attached to the catalytic part. Antibodies against calmodulin inhibited the enzyme as did La3+ and EGTA. AC activity appeared to be regulated specifically by K+, enzyme activity being enhanced up to 100% by 15 mM K+. Na+ and Li+ were inactive.
The crystal structure of pseudoazurin from Alcaligenes faecalis S‐6 determined at 2.9 Å resolution
Authors: Petratos K. , Banner D.W. , Beppu T. , Wilson K.S. , Tsernoglou D.
Published: July 2002

The three‐dimensional structure of pseudoazurin, a single copper‐containing protein from Alcaligenes faecalis strain S‐6, has been determined at 2.9 Å resolution by X‐ray crystallography. The sequences of two other pseudoazurins from Pseudomonas AMl and Achromobacter cycloclastes may also be accommodated in this structure. The structure, an eight‐stranded β‐barrel, resembles closely those of plastocyanin and azurin. It possesses two extra α‐helices at the C‐terminus, whereas azurins have an α‐helical flap in the middle of their sequences.
Tau factor polymers are similar to paired helical filaments of Alzheimer's disease
Authors: de Garcini Esteban Montejo , Carrascosa José L. , Correas Isabel , Nieto Amelia , Avila Jesús
Published: July 2002

Tau factor, upon urea treatment, is able to polymerize in vitro. These polymers are composed of tau factor as shown by immunogold staining. The structure of tau polymers is very similar to that of paired helical filaments (PHFs) of Alzheimer's disease in their dimensions as well as in their periodicity. Metal shadowing of both polymers shows a similar twisting. Also, similar peptide maps were found for tau factor and a 33 kDa protein that is the main component of our PHF preparations.
Hormone‐sensitive lipase is responsible for the neutral cholesterol ester hydrolase activity in macrophages
Authors: Small Catherine A. , Goodacre John A. , Yeaman Stephen J.
Published: July 2002

Anti‐hormone‐sensitive lipase (HSL) immunoglobulin selectively immunoprecipitates a single 84 kDa 32P‐phosphoprotein from macrophage homogenates previously phosphorylated by cyclic AMP‐dependent protein kinase in the presence of [γ‐32P]ATP‐Mg. This immunoglobulin also completely removes the neutral cholesterol ester hydrolase activity from macrophage homogenates. These data demonstrate that HSL is responsible for the neutral cholesterol ester hydrolase activity in macrophages and hence plays a key role in cholesterol metabolism in these cells.
The crystal structure of human muscle aldolase at 3.0 Å resolution
Authors: Gamblin S.J. , Cooper B. , Millar J.R. , Davies G.J. , Littlechild J.A. , Watson H.C.
Published: July 2002

The three‐dimensional structure of fructose‐1,6‐bisphosphate aldolase from human muscle has been determined at 3.0 Å resolution by X‐ray crystallography. The active protein is a tetramer of 4 identical subunits each of which is composed of an eight‐stranded α/β‐barrel structure. The lysine residue responsible for Schiff base formation with the substrate is located near the centre of the barrel in the middle of the sixth β‐strand. While the overall topology of the α/β‐barrel is very similar to those found in several other enzymes, the distribution of charged residues inside the core of the barrel seems distinct. The quaternary fold of human muscle aldolase uses interfacial regions also involved in the subunit association of other α/β‐barrel proteins found in glycolysis, but exploits these regions in a manner not seen previously.
The phosphorylation of the two‐chain form of vitronectin by protein kinase A is heparin dependent
Authors: Chain Daniel , Korc-Grodzicki Beatriz , Kreizman Tamar , Shaltiel Shmuel
Published: July 2002

In circulating blood, vitronectin occurs in two forms: a single‐chain (75 kDa) and an endogenously clipped two‐chain form (65 kDa and 10 kDa) held together by a disulfide bridge. The 75 kDa form was previously shown to be phosphorylated at Ser378 by protein kinase A, released by physiologically stimulated platelets. By contrast, at pH 7.5 the two‐chain form is not phosphorylated at all. Heparin or heparan sulfate are shown here to modulate the conformation of clipped vitronectin at physiological pH, exposing Ser378 and allowing its stoichiometric phosphorylation by the kinase. At this pH the two‐chain form of vitronectin in plasma exhibits a higher affinity for heparin, and behaves as a flexible molecule, which can conformationally respond to heparin and heparan sulfate, effectors involved in vitronectin function.
Antithrombin Rouen‐IV 24 Arg→Cys The amino‐terminal contribution to heparin binding
Authors: Borg J.-Y. , Brennan S.O. , Carrell R.W. , George P. , Perry D.J. , Shaw J.
Published: July 2002

A variant antithrombin with reduced heparin affinity was shown by mass spectrometry sequencing and DNA amplification to have a substitution of a cysteine for an arginine at residue 24. The position of Arg‐24 can be fixed within a 12 Å radius from the bridge at Cys‐21. This is compatible with findings in the homologous protease nexin‐1 which indicate an extension of the binding site of heparin from the D‐helix to under the adjacent amino‐terminal pole.
Electron spin resonance study on the permeability of superoxide radicals in lipid bilayers and biological membranes
Authors: Mao Guo Dong , Poznansky Mark J.
Published: July 2002

The permeability of lipid bilayers and biological membranes to superoxide free radicals was examined by using superoxide dismutase (SOD)‐loaded lipid vesicles and SOD‐loaded erythrocyte ghosts. After exposing SOD lipid vesicles and SOD ghosts to enzymatically produced superoxide radicals and using spin‐trapping and electron spin resonance (ESR) techniques, we found that SOD entrapped within erythrocyte ghosts effectively scavenges external O.−
2 while SOD inside the lipid bilayers has no effect. These results confirm that O.−
2 is able to cross through a biological plasma membrane but not across a pure lipid bilayer. The data provide instruction as to how and where anti‐oxidant therapy is to be approached relative to the site of oxygen free radical production.
Modification by site‐directed mutagenesis of the specificity of Erythrina corallodendron lectin for galactose derivatives with bulky substituents at C‐2
Authors: Arango Rafael , Rodriguez-Arango Esperanza , Adar Rivka , Belenky David , Loontiens Frank G. , Rozenblatt Shmuel , Sharon Nathan
Published: July 2002

Examination of the three‐dimensional structure of Erythrina corallodendron lectin (ECorL) in complex with a ligand (lactose), the first of its kind for a Gal/GalNAc‐specific lectin [(1991) Science 254, 862‐866], revealed the presence of a hydrophobic cavity, surrounded by Tyr108 and Pro134‐Trp135, which can accommodate bulky substituents such as acetamido or dansylamido (NDns) at C‐2 of the lectin‐bound galactose. Comparison of the primary sequence of ECorL with that of soybean agglutinin, specific for galactose and its C‐2 substituted derivatives, and of peanut agglutinin, specific for galactose only, showed that in soybean agglutinin, Tyr108 is retained, and Pro134‐Trp135 is replaced by Ser‐Trp, whereas in peanut agglutinin, the former residue is replaced by Thr and the dipeptide by Ser‐Glu‐Tyr‐Asn. Three mutants of ECorL were therefore constructed: L2, in which Pro134‐Trp135 was replaced by Ser‐Glu‐Tyr‐Asn; Y108T, in which Tyr108 was replaced by Thr and the double mutant L2; Y108T. They were expressed in Escherichia coli, as done for recombinant ECorL [(1992) Eur. J. Biochem. 205, 575‐581]. The mutants had the same hemagglutinating activity as native or rECorL. Their specificity for galactose, GalNAc and MeβGalNDns was examined by inhibition of hemagglutination and of the binding of the lectin to immobilized asialofetuin; in addition, their association constants with MeαGalNDns and MeβGalNDns were measured by spectrofluorimetric titration. The results showed that Y108T had essentially similar specificity as the native and recombinant lectins. The affinity of L2 and L2;Y108T for galactose was also the same as ECorL, but they had a lower affinity for GalNAc and markedly diminished affinity for the dansyl sugars (up to 43 times, or 2 kcal, less). This appears to be largely due to steric hindrance by the two additional amino acids present in the cavity region in these mutants. Our findings also provide an explanation for the inability of PNA to accommodate C‐2‐substituted galactose derivatives at its primary subsite.
The 5' untranslated region of the human γ‐glutamyl transferase mRNA contains a tissue‐specific active translational enhancer
Authors: Diederich Marc , Wellman Maria , Visvikis Athanase , Puga Alvaro , Siest Gérard
Published: July 2002

We report the functional and structural analysis of the 5' untranslated region (5'UTR) of human hepatoma HepG2 γ‐glutamyltransferase (GGT) mRNA. Transient expression of a hybrid GGT‐luciferase gene in HepG2, MIA‐Pa‐Ca‐2 and MG 63 cell lines shows that this 5'UTR acts as a tissue‐specific translational enhancer. Evidence for transcripts with multiple 5'UTR coding for HepG2 GGT was obtained by RNase protection. Computer analysis of this 5'UTR detected the existence of a stable stem and loop structure containing multiple steroid modulatory elements.
Core sequence of ATP regulatory module in receptor guanylate cyclases
Authors: Duda Teresa , Goraczniak Rafal M. , Sharma Rameshwar K.
Published: July 2002

Atrial natriuretic factor (ANF) and C‐type natriuretic peptide (CNP)‐activated guanylate cyclases are single‐chain transmembrane‐spanning proteins, containing both ligand binding and catalytic activities. In both proteins, ligand binding to the extracellular receptor domain activates the cytosolic catalytic domain, generating the second messenger cyclic GMP. Studies with ANF receptor guanylate cyclase (ANF‐RGC) have indicated that obligatory in this activation process is an ATP‐dependent step. ATP directly binds to the cyelase and bridges the events of ligand binding and signal transduction. A defined ATP‐regulated module (ARM) sequence (Gly503‐Arg‐Gly‐Ser‐Asn‐Tyr‐Gly509) in the cyclase is critical in the ATP‐mediated event. Through genetic remodeling techniques, we have now identified the core ARM sequence that is essential in both ANF and CNP signaling. This sequence is Gly‐Xa‐Xa‐Xa‐Gly, represented by Gly505‐Ser‐Asn‐Tyr‐Gly509 in the case of ANF‐RGC ARM and by Gly499‐Ser‐Ser‐Tyr‐Gly503 in the CNP receptor guanylate cyclase ARM.
Identification of serines‐1035/1037 in the kinase domain of the insulin receptor as protein kinase Cα mediated phosphorylation sites
Authors: Liu Feng , Roth Richard A.
Published: July 2002

A new site of serine phosphorylation (Ser‐1035/1037) has been identified in the kinase domain of the insulin receptor. Mutant receptors missing these two serines were expressed in Chinese hamster ovary cells overexpressing protein kinase Cα. These mutant receptors lacked a phorbol ester‐stimulated phosphoserine containing tryptic peptide as demonstrated by both high percentage polyacrylamide/urea gel electrophoresis and two‐dimensional tlc. Moreover, a synthetic peptide with the sequence of this tryptic peptide was phosphorylated by isolated protein kinase Cα, and co‐migrated with the phosphopeptide from in vivo labeled receptor. These results indicate that serine‐1035 and/or 1037 in the kinase domain of the insulin receptor are phosphorylated in response to activation of protein kinase Cα.
Solution structure of ω‐conotoxin MVIIA using 2D NMR spectroscopy
Authors: Basus Vladimir J. , Nadasdi Laszlo , Ramachandran J. , Miljanich George P.
Published: July 2002

The solution structure of ω‐conotoxin MVIIA (SNX‐111), a peptide toxin from the fish hunting cone snail Conus magus and a high‐affinity blocker of N‐type calcium channels, was determined by 2D NMR spectroscopy. The backbones of the best 44 structures match with an average pairwise RMSD of 0.59 angstroms. The structures contain a short segment of triple‐stranded β‐sheet involving residues 6–8, 20–21, and 24–25. The structure of this toxin is very similar to that of ω‐conotoxin GVIA with which is has only 40% sequence homology, but very similar calcium channel binding affinity and selectivity.
Neurotrophic effect of hematopoietic cytokines on cholinergic and other neurons in vitro
Authors: Tabira T. , Konishi Y. , Gallyas F.
Published: July 2002

We examined the effects of interleukin‐3 (IL‐3) and other hematopoietic cytokines on the neurotransmitters, neurite formation, and differentiation in cholinergic and other types of neurons. IL‐3, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), macrophage colony‐stimulating factor, granulocyte colony‐stimulating factor and erythropoietin (Epo) elevated choline acetyltransferase (ChAT) activity in septal cholinergic cell line SN6 as well as in primary cultured septal neurons without increasing protein contents of the cells. These effects were dose‐dependent and the optimal doses were not different from those for blood cells. IL‐3 had neurite‐promoting activity but GM‐CSF had no such effect. Both IL‐3 and GM‐CSF decreased intracellular acetylcholine concentration, and elevated glutamic acid decarboxylase and intracellular GABA in septal neuronal cultures. Epo elevated monoamines in PC12 cells. These effects are thought to result from direct action through their specific receptors in neurons, because (i) anti‐IL‐3‐receptor antibody abolished the ChAT activity in septal neurons increased by IL‐3; (ii) mRNA and immunoreactivity for β subunits of IL‐3 receptors were expressed in septal cholinergic neurons and (iii) presence of receptos for GM‐CSF and Epo in neurons has been reported. Our observation and others strongly support that neural‐immune interactions are important not only in the defense mechanism in the nervous system but also in the development, differentiation and function of neurons.
Retinoic acid induces cholinergic differentiation of NTera 2 human embryonal carcinoma cells
Authors: Zeller Markus , Strauss William L.
Published: July 2002

Retinoic acid (RA), a natural metabolite of vitamin A, influences the survival and neurotransmitter phenotype of several classes of vertebrate neurons during development. We now report that RA induces a subpopulation of NTera 2/clone D1 (NT2) human embryonal carcinoma cells to differentiate into postmitotic cells with cholinergic properties (NT2‐N cells). After growth for 6 days in the presence of RA (10 μM) low levels of the acetylcholine‐synthesizing enzyme choline acetyltransferase (ChAT) were detected in NT2 cell cultures. ChAT activity in the NT2 cell cultures continued to increase for at least an addition 22 days to a final activity of 50 pmol ACh synthesized/min/mg protein. Immunohistochemical staining of RA‐treated cultures demonstrated that only those cells with a neuronal morphology (NT2‐N cells) expressed the human ChAT protein. Since such cells comprised a small proportion (∼20%) of the population, the ChAT activity per neuronal cell was estimated to approach 250–300 pmol ACh/min/mg protein. Cultures composed of >95% NT2‐N cells had significantly lower ChAT specific activities and this could be increased by either ciliary neurotrophic factor or leukemia inhibitory factor, but not by nerve growth factor. We conclude that NT2 cells provide a system in which to study the molecular events that underlie neurotransmitter choice during the differentiation of human cholinergic neurons.
A small deletion on the short arm of chromosome 18 in a female schizophrenic patient
Authors: De Marchi N , Vicari L , D'Agostino F
Published: July 2002

The authors describe the occurrence of a small deletion localised on the short arm of chromosome 18 in a young female with a diagnosis of paranoid schizophrenia.
Comorbidity in obsessive-compulsive disorder: focus on depression
Authors: Milanfranchi A , Marazziti D , Pfanner C , Presta S , Lensi P , Ravagli S , Cassano GB
Published: July 2002

The authors investigated the comorbidity between obsessive-compulsive disorder (OCD) and other psychiatric disorders in a group of 154 outpatients. The influence of an associate major depressive disorder (MDD) on the outcome of treatment with clomipramine was examined in a subgroup of 52 patients. The results showed that MDD was the most frequent disorder associated with OCD (almost 20% of the patients), followed by generalized anxiety and panic disorder. The co-presence of depression delayed the effect of clomipramine.
The molecular basis for genetic polymorphism of human deoxyribonuclease II (DNase II): a single nucleotide substitution in the promoter region of human DNase II changes the promoter activity
Authors: Yasuda Toshihiro , Takeshita Haruo , Nakazato Emiko , Nakajima Tamiko , Nakashima Yoshimitsu , Mori Shinjiro , Mogi Kouichi , Kishi Koichiro
Published: July 2002

Deoxyribonuclease II (DNase II) levels in human vary depending on whether the individual has the DNASE2*H (high) allele or the DNASE2*L (low) allele. We examined the promoter activity of the 5′‐flanking region of each of these alleles by transient transfection luciferase assay. DNASE2*H had 5‐fold higher promoter activity than DNASE2*L in human hepatoma HepG2 cell. Comparison of the nucleotide sequences of the proximal promoter regions revealed a G to A transition at position −75; G and A residues were assigned to DNASE2*H and *L, respectively. Since no differences were found between the open reading frame sequences of these alleles, it is likely that the A−75G transition causes the allelic difference in the promoter activity of the gene, underlying the genetic polymorphism.
Properties of an insulin receptor with an IGF‐1 receptor loop exchange in the cysteine‐rich region
Authors: Hoyne Peter A , Elleman Thomas C , Adams Timothy E , Richards Kim M , Ward Colin W
Published: July 2002

The insulin receptor (IR) and the insulin‐like growth factor‐I receptor (IGF‐1R) show differential binding of insulin and IGFs. The specificity determinants for IGF‐1 binding are known to be located in the cysteine‐rich (Cys‐rich) region between residues 223 and 274 of human IGF‐1R, which includes a loop that protrudes into the putative ligand binding site. In this report we have replaced residues 260–277 of human IR with residues 253–266 of the human IGF‐1R to produce an IR‐based, cysteine loop exchange chimaera, termed hIR‐Cys loop exchange (CLX), in which all 14 amino acid residues in the exchanged loop differ from wild‐type insulin receptor. This loop exchange had a detrimental effect on the efficiency of pro‐receptor processing and on the binding of the mouse monoclonal antibody 83‐7. However, this antibody, which binds hIR but not hIGF‐1R, was still capable of immunoprecipitating the mature chimaeric receptor, indicating that the conformational epitope recognised by this antibody is not primarily determined by the loop region exchanged. The loop exchange did not significantly affect the ability of insulin to displace bound radiolabelled insulin, but increased the capacity of IGF‐1 to competitively displace labelled insulin by at least 10 fold.
Identification of group X secretory phospholipase A2 as a natural ligand for mouse phospholipase A2 receptor
Authors: Yokota Yasunori , Higashino Ken-ichi , Nakano Kazumi , Arita Hitoshi , Hanasaki Kohji
Published: July 2002

Phospholipase A2 receptor (PLA2R) mediates various biological responses elicited by group IB secretory phospholipase A2 (sPLA2‐IB). The recently cloned group X sPLA2 (sPLA2‐X) possesses several structural features characteristic of sPLA2‐IB. Here, we detected a specific binding site of sPLA2‐X in mouse osteoblastic MC3T3‐E1 cells. Cross‐linking experiments demonstrated its molecular weight (180 kDa) to be similar to that of PLA2R. In fact, sPLA2‐X was found to bind the recombinant PLA2R expressed in COS‐7 cells, and its specific binding detected in mouse lung membranes was abolished by the deficiency of PLA2R. These findings demonstrate sPLA2‐X to be one of the high‐affinity ligands for mouse PLA2R.
Purification, cDNA cloning and function assessment of BmK abT, a unique component from the Old World scorpion species
Authors: Ye Jian-Guo , Wang Cong-Ying , Li Ya-Jun , Tan Zhi-Yong , Yan Yan-Ping , Li Chen , Chen Jin , Ji Yong-Hua
Published: July 2002

A new neurotoxic component named BmK abT was purified from the venom of Chinese scorpion Buthus martensi Karsch. The molecular weight of BmK abT was determined to be 7212 Da on a mass spectrum. The minimum lethal dose of BmK abT was tested to be about 1.5 μg per mouse by intracerebroventricular injection, and the dose induced significant paralysis effect on cockroach was about 5 μg by i.p. injection. The partial amino acid sequence indicated that it was a distinctive polypeptide in the scorpion neurotoxin family. Thereafter, the whole amino acid sequence of mature BmK abT was deduced from cDNA sequence by 5′‐ and 3′‐rapid amplification of cDNA ends. Finally, it was defined to be composed of 63 residues with amidation at the C‐terminal residue. By sequence comparison, BmK abT was found to be most similar to Ts VII, a β‐toxin from the New World scorpion. The patch‐clamp recording on DRG neurons, unexpectedly, showed this toxin could prolong the action potential and increase the amplitude of the peak Na+ currents, which are the typical characters of α‐toxin. These results suggested that BmK abT was a new toxic component found in the Old World scorpion species structurally similar to β‐toxins, but functionally similar to α‐toxins.
Human fibulin‐4: analysis of its biosynthetic processing and mRNA expression in normal and tumour tissues
Authors: Gallagher William M. , Greene Lisa M. , Ryan Michael P. , Sierra Véronique , Berger Anne , Laurent-Puig Pierre , Conseiller Emmanuel
Published: July 2002

Here, we report the identification of a human orthologue of fibulin‐4, along with analysis of its biosynthetic processing and mRNA expression levels in normal and tumour tissues. Comparative sequence analysis of fibulin‐4 cDNAs revealed apparent polymorphisms in the signal sequence that could account for previously reported inefficient secretion in fibulin‐4 transfectants. In vitro translation of fibulin‐4 mRNA revealed the presence of full‐length and truncated polypeptides, the latter apparently generated from an alternative translation initiation site. Since this polypeptide failed to incorporate into endoplasmic reticulum membrane preparations, it was concluded that it lacked a signal sequence and thus could represent an intracellular form of fibulin‐4. Using fluorescence in situ hybridisation analysis, the human fibulin‐4 gene was localised to chromosome 11q13, this region being syntenic to portions of mouse chromosomes 7 and 19. Considering the fact that translocations, amplifications and other rearrangements of the 11q13 region are associated with a variety of human cancers, the expression of human fibulin‐4 was evaluated in a series of colon tumours. Reverse transcription‐polymerase chain reaction analysis of RNA from paired human colon tumour and adjacent normal tissue biopsies showed that a significant proportion of tumours had ∼2–7‐fold increases in the level of fibulin‐4 mRNA expression. Taken together, results reported here suggest that an intracellular form of fibulin‐4 protein may exist and that dysregulated expression of the fibulin‐4 gene is associated with human colon tumourigenesis.
Mitochondrial DNA deletions in oculopharyngeal muscular dystrophy
Authors: Lezza Angela M.S , Cormio Antonella , Gerardi Patrizia , Silvestri Gabriella , Servidei Serena , Serlenga Luigi , Cantatore Palmiro , Gadaleta Maria Nicola
Published: July 2002

The deletions in the mitochondrial DNA from skeletal muscle samples of two oculopharyngeal muscular dystrophy cases were studied using polymerase chain reaction techniques. The 4977 bp `common deletion' was present in both specimens, exceeding the corresponding values of similarly aged, healthy controls. In the two samples multiple different mitochondrial DNA deletions, some case‐specific and present at quite high, although not pathogenetic levels, were observed. The results suggest that mitochondrial DNA deletions, and the `common deletion' in particular, might be a sensitive and early marker of a generalized mitochondrial suffering, due to a variety of pathological and physiological causes.
Structural dynamics of the Streptomyces lividans K+ channel (SKC1): secondary structure characterization from FTIR spectroscopy
Authors: Tatulian Suren A. , Cortes D.Marien , Perozo Eduardo
Published: July 2002

Fourier transform infrared (FTIR) spectroscopy was used to probe the secondary structure, orientation, and the kinetics of amide hydrogen‐deuterium exchange (HX) of the small K+ channel from Streptomyces lividans. Frequency component analysis of the amide I band showed that SKC1 is composed of 44–46% α‐helix, 21–24% β‐sheet, 10–12% turns and 18–20% unordered structures. The order parameter S of the helical component of SKC1 was between 0.60 and 0.69. Close to 80% of SKC1 amide protons exchange within ∼3 h of D2O exposure, suggesting that the channel is largely accessible to solvent exchange. These results are consistent with a model of SKC1 in which helices slightly tilted from the membrane normal line the water‐filled vestibules that flank the K+ selectivity filter.
Transcriptional regulation of the heavy subunit chain of γ‐glutamylcysteine synthetase by ionizing radiation
Authors: Morales Albert , Miranda Merce , Sanchez-Reyes Alberto , Colell Anna , Biete Albert , Fernández-Checa José C
Published: July 2002

Since glutathione (GSH) protects against oxidative stress, we determined the regulation of cellular GSH by ionizing radiation in human hepatoblastoma cells, HepG2. The levels of GSH increased in irradiated HepG2 due to a greater γ‐glutamylcysteine synthetase (γ‐GCS) activity, which was paralleled by γ‐GCS heavy subunit chain (γ‐GCS‐HS) mRNA levels. Transcription of deletion constructs of the γ‐GCS‐HS promoter cloned in a reporter vector was associated with activator protein‐1 (AP‐1), consistent with the DNA binding of AP‐1 in nuclear extracts of irradiated HepG2. Hence, the transcriptional regulation of γ‐GCS by ionizing radiation emerges as an adaptive mechanism, which may be of significance to control the consequences of the oxidative stress induced by radiation.
Purification and characterization of a novel glycine oxidase from Bacillus subtilis
Authors: Nishiya Yoshiaki , Imanaka Tadayuki
Published: July 2002

The open reading frame yjbR which had been sequenced as a part of the Bacillus subtilis genome project encodes a putative 40.9‐kDa protein. The yjbR‐coding sequence was slightly similar to those of bacterial sarcosine oxidases and possibly compatible with the tertiary structure of the porcine kidney d‐amino acid oxidase. The yjbR gene product was overproduced in Escherichia coli, purified to homogeneity from the recombinant strain, and characterized. This protein effectively catalyzed the oxidation of sarcosine (N‐methylglycine), N‐ethylglycine and glycine. Lower activities on d‐alanine, d‐valine, and d‐proline were detected although no activities were shown on l‐amino acids and other d‐amino acids. Since glycine is a product and not a substrate for sarcosine oxidase, this protein is not a type of demethylating enzymes but a novel deaminating oxidase, named glycine oxidase as a common name. Several enzymatic properties of the B. subtilis glycine oxidase were also investigated.
Identification of a human mitochondrial ABC transporter, the functional orthologue of yeast Atm1p
Authors: Csere Peter , Lill Roland , Kispal Gyula
Published: July 2002

We have sequenced the entire coding region of the human ABC transporter ABC7. The protein represents a ‘half‐transporter' and displays high sequence similarity to the mouse ABC7 protein and to the mitochondrial ABC transporter Atm1p of Saccharomyces cerevisiae. As shown by immunostaining using a specific antibody, the human ABC7 protein (hABC7) is a constituent of mitochondria. The N‐terminus of hABC7 contains the information for targeting and import into the organelles. When synthesised in yeast cells defective in Atm1p (strain Δatm1/hABC7), hABC7 protein can revert the strong growth defect observed for Δatm1 cells to near wild‐type behaviour. The known phenotypical consequences of inactivation of the ATM1 gene are almost fully amended by expression of hABC7 protein. Δatm1/hABC7 cells harbour wild‐type levels of cytochromes and extra‐mitochondrial heme‐containing proteins, they contain normal levels of mitochondrial iron, and the cellular content of glutathione is substantially reduced relative to the high levels detected in Δatm1 cells. Our results suggest that hABC7 is a mitochondrial protein, and represents the functional orthologue of yeast Atm1p.
Receptor activator of NF‐κB recruits multiple TRAF family adaptors and activates c‐Jun N‐terminal kinase
Authors: Kim Hong-Hee , Lee Da Eun , Shin Jin Na , Lee Yong Soo , Jeon Yoo Mi , Chung Chae-Heon , Ni Jian , Kwon Byoung Se , Lee Zang Hee
Published: July 2002

Receptor activator of NF‐κB (RANK) is a recently cloned member of the tumor necrosis factor receptor (TNFR) superfamily, and its function has been implicated in osteoclast differentiation and dendritic cell survival. Many of the TNFR family receptors recruit various members of the TNF receptor‐associated factor (TRAF) family for transduction of their signals to NF‐κB and c‐Jun N‐terminal kinase. In this study, the involvement of TRAF family members and the activation of the JNK pathway in signal transduction by RANK were investigated. TRAF1, 2, 3, 5, and 6 were found to bind RANK in vitro. Association of RANK with each of these TRAF proteins was also detected in vivo. Expression of RANK in cultured cells also induced the activation of JNK, which was blocked by a dominant‐negative form of JNK. Furthermore, by employing various C‐terminal deletion mutants of RANK, the regions responsible for TRAF interaction and JNK activation were identified. TRAF5 was determined to bind to the C‐terminal 11 amino acids and the other TRAF members to a region N‐terminal to the TRAF5 binding site. The domain responsible for JNK activation was localized to the same region where TRAF1, 2, 3, and 6 bound, which suggests that these TRAF molecules might mediate the RANK‐induced JNK activation.
Nucleotide binding to creatine kinase: an isothermal titration microcalorimetry study
Authors: Forstner Michael , Berger Christine , Wallimann Theo
Published: July 2002

We investigated the binding of ATP in the presence and absence of Mg2+ to dimeric muscle creatine kinase (CK) by isothermal titration microcalorimetry as a function of pH and temperature. The thermodynamic parameters for these events show that (1) binding of nucleotide to the CK active site does not involve proton exchange with the buffer and (2) the active sites are the only nucleotide binding sites on CK. Interdependence of the active sites in the dimer could not be demonstrated. As CK undergoes major structural changes upon Mg‐nucleotide binding, a thermodynamic cycle was employed to calculate the contributions of domain movements to the observed enthalpies.
Bacterial vaginosis and contraceptive methods
Authors: Calzolari E , Masciangelo R , Milite V , Verteramo R
Published: July 2002

Objective: The aim of this study was to investigate if bacterial vaginosis is associated with the use of specific contraceptives. Methods: The study population consisted of 1314 women attending for periodical preventive examinations at our gynecology unit at the II Institute of Obstetrics and Gynecology of the University ‘La Sapienza’ in Rome. The patient's history and any current genital symptom were recorded on a structured protocol. Current users of contraceptives were compared with non‐users. The χ2 test and the t‐test were used in the statistical analysis; a stepwise logistic regression analysis was performed to assess the simultaneous effect of more than one variable and to identify for possible confounding factors. Results: Both oral contraceptive and condom use showed a significant protective effect against bacterial vaginosis. Our results also showed a significant increase of BV among IUD users, either before or after adjustments. Conclusions: This study showed a significant negative association between BV and OC and condom use, respectively, and a significant positive association between BV and IUD use. Therefore, we suggest that it is advisable to carry out a systematic microscopic evaluation in order to identify BV for IUD users.
Working conditions and prevalence of pre‐eclampsia, Norway 1989
Authors: Wergeland E. , Strand K.
Published: July 2002

Objective: To study the associations between working conditions and pre‐eclampsia. Methods: A cross‐sectional study based on questionnaires to all parturients was conducted in Norway from 16 October 1989 to 26 November 1989, with an 87.2% response rate. Of the 5388 responders with singleton pregnancies, 3321 continued in paid work beyond the 3rd month of pregnancy. Pre‐eclampsia was recorded if the woman reported hospitalization for hypertension, or if proteinuria and hypertension were diagnosed more than once in the pregnancy. Results: The prevalence of pre‐eclampsia was increased in work involving the lifting of heavy loads of 10–20 kg (adjusted odds ratio (OR), 1.8; 95% CI, 1.2–2.5), hectic work pace (OR, 1.4; 95% CI, 1.0–2.0, P < 0.05), work with hands above shoulder level (OR, 1.4; 95% CI, 1.0–2.2; P = 0.07) and for parous women, shift work (OR, 2.0; 95% CI, 1.1–3.6). It was reduced when the woman had an influence on work pace (OR, 0.7; 95% CI, 0.5–1.0; P = 0.07). Prevalence was also increased with daily consumption of more than four cups of coffee (OR, 1.6; 95% CI, 1.1–2.3). Conclusion: Prenatal care should include assessment of working conditions, as early improvements may reduce the risk of pre‐eclampsia.
Strategically managed buyer–supplier relationships and performance outcomes
Authors: Carr Amelia S , Pearson John N
Published: July 2002

An empirical analysis of purchasing's strategic role in the firm is presented. This study uses data collected from high level purchasing executives at the Director/VP level representing a large cross industry sample of 739 firms. The data analysis is rigorous. Using data from 571 of the 739 firms, correlation analysis and exploratory factor analysis is performed. Data from the remaining 168 firms is used to conduct structural equation modeling. This is the first attempt to examine a structural model of strategic purchasing and its influence on supplier evaluation systems, buyer–supplier relationships, and firm's financial performance. Scales are developed to measure each construct and are shown to be reliable. Five hypothesized relationships are presented and supported by the literature. The first, second, and third hypotheses link strategic purchasing to supplier evaluation systems, buyer–supplier relationships and firm's financial performance, respectively. The fourth hypothesis links supplier evaluation systems to buyer–supplier relationships. And, the fifth hypothesis links buyer–supplier relationships to firm's financial performance. The results of the data analysis provide support for each of the five hypotheses above. The implications of this research are that a strategic purchasing function is important to the success of the firm. Firms that have a strategic purchasing function are more likely to implement a supplier evaluation system. This provides purchasing with a better understanding of which suppliers are performing well and which suppliers are not performing well. Increased emphasis on strategic purchasing and supplier evaluation systems are critical for firms seeking to establish long‐term relationships with their suppliers. Based on the findings of this study, strategically managed long‐term relationships with key suppliers can have a positive impact on the firm's financial performance.
Behavioral symptoms in adult rats after postnatal l‐nitro‐arginine
Authors: Wörtwein Gitta , Gustafson Bettina , Hansen Karina Liv , Mogensen Jesper
Published: July 2002

We addressed experimentally the suggestion by Gally et al. [Gaily J. A., Read Montague P., Reeke G. N. Jr and Edelman G. M. (1990) Proc. Natl Acad. Sci. U.S.A.87, 3547–3551] that nitric oxide may play a role in the use‐dependent modification of synaptic efficacy in the developing nervous system. In a preliminary control experiment, we treated rat pups from postnatal day 8 to postnatal day 22 with a nitric oxide synthase blocker (l‐nitro‐arginine) and compared their growth curves and brain weights to those of saline injected control pubs. No significant differences were found after the 14 days of nitric oxide synthase inhibition. In the subsequent experiment, we inhibited nitric oxide synthesis in rat pups from postnatal day 8 to day 29 and assessed their place learning ability and open field behavior as adults. We found an increased speed of habituation of locomotion in an open field in 5‐month‐old rats that had been treated postnatally with a nitric oxide synthase blocker. There was no difference between treated and nontreated rats with respect to place learning in a water maze. We conclude that perturbation of nitric oxide production during early postnatal development does not preclude normal learning and memory function in the adult.
Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences
Authors: Benabarre A. , Vieta E. , Colom F. , Martínez-Arán A. , Reinares M. , Gastó C.
Published: July 2002

The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.
Ethnic differences in the presentation of bipolar affective disorder
Authors: Kirov G. , Murray R.M.
Published: July 2002

There have been repeated reports that Afro-Caribbean people living in the UK are more prone than white people to be diagnosed as having schizophrenia and mania, along with some evidence that they are less likely to receive a diagnosis of depression. We attempted to replicate these findings in a population of patients on lithium prophylaxis. We therefore assessed the clinical characteristics of people under the age of 55 from three ethnic groups attending a lithium clinic in south London, those of (1) white British (n = 88); (2) Afro-Caribbean (n = 31); and, (3) African (n = 15) origin.

Nineteen of the white patients met DSM-IV criteria for unipolar depression (UP) and eight met the criteria for bipolar II disorder (BP II); in contrast, only two black patients met the criteria for unipolar depression and none met the criteria for BP II. Among patients diagnosed as BP I, Africans were significantly more likely than whites to show exclusively or mainly manic presentations while Afro-Caribbeans were more likely to have had mood-incongruent delusions. On the other hand, white patients were significantly more likely than Afro-Caribbeans to have had suicidal ideas or actions, and showed a similar but not significant excess when compared with Africans.

Our findings could reflect either genuine ethnic differences in the presentation of severe affective disorder or be produced by the failure of British doctors to detect depression and deliver appropriate treatment to their black patients. The frequency with which Afro-Caribbean patients with mania present mood-incongruent delusions probably contributes to the high rates of diagnosed schizophrenia in this population.