bluuebunny/crossref_metadata_2025 huggingface dataset:
RAC‐3 is a NF‐κB coactivator
Authors: Werbajh Santiago , Nojek Ignacio , Lanz Rainer , Costas Mónica A.
Published: July 2002

It has been shown that the molecular mechanism by which cytokines and glucocorticoids mutually antagonize their functions involves a mutual glucocorticoid receptor (GR)/nuclear factor‐κB (NF‐κB) transrepression. Here we report a role for the nuclear receptor coactivator RAC3, in modulating NF‐κB transactivation. We found that RAC3 functions as a coactivator by binding to the active form of NF‐κB and that overexpression of RAC3 restores GR‐dependent transcription neglecting GR/NF‐κB transrepression. The competition between GR and NF‐κB for binding to RAC3 may represent a general mechanism by which both transcription factors mutually antagonize their activity.
Relationship between DNA methylation, histone H4 acetylation and gene expression in the mouse imprinted Igf2‐H19 domain
Authors: Grandjean Valerie , O'Neill Laura , Sado Takashi , Turner Bryan , Ferguson-Smith Anne
Published: July 2002

DNA methylation and histone H4 acetylation play a role in gene regulation by modulating the structure of the chromatin. Recently, these two epigenetic modifications have dynamically and physically been linked. Evidence suggests that both modifications are involved in regulating imprinted genes – a subset of genes whose expression depends on their parental origin. Using immunoprecipitation assays, we investigate the relationship between DNA methylation, histone H4 acetylation and gene expression in the well‐characterised imprinted Igf2‐H19 domain on mouse chromosome 7. A systematic regional analysis of the acetylation status of the domain shows that parental‐specific differences in acetylation of the core histone H4 are present in the promoter regions of both Igf2 and H19 genes, with the expressed alleles being more acetylated than the silent alleles. A correlation between DNA methylation, histone hypoacetylation and gene repression is evident only at the promoter region of the H19 gene. Treatment with trichostatin A, a specific inhibitor of histone deacetylase, reduces the expression of the active maternal H19 allele and this can be correlated with regional changes in acetylation within the upstream regulatory domain. The data suggest that histone H4 acetylation and DNA methylation have distinct functions on the maternal and paternal Igf2‐H19 domains.
Influence of oocyte nuclei on demethylation of donor genome in cloned bovine embryos
Authors: Kang Yong-Kook , Koo Deog-Bon , Park Jung-Sun , Choi Young-Hee , Lee Kyung-Kwang , Han Yong-Mahn
Published: July 2002

We recently demonstrated that satellite regions exhibit an aberrant DNA methylation in cloned bovine embryos. Here, we examined, using bisulfite‐sequencing technology, whether the inefficient demethylation of cloned donor genomes could be rescued by the presence of oocytic nuclei. Both AciI digestion and sequencing analyses showed that satellite sequence was demethylated more efficiently in cloned tetraploid blastocysts than in diploid clones. When methyl‐CpG density (the number of methyl‐CpG sites per string) was scored, a significant decrease was observed in tetraploids (P<0.001). These results suggest that unknown mechanisms provided by oocytic nuclei could assist the demethylation of satellite sequences in tetraploid clones.
cDNA cloning, sequence analysis and allergological characterization of Par j 2.0101, a new major allergen of the Parietaria judaica pollen
Authors: Duro Giovanni , Colombo Paolo , Costa Maria Assunta , Izzo Vincenzo , Porcasi Rossana , Di Fiore Renata , Locorotondo Giovanni , Mirisola Mario G. , Cocchiara Roberta , Geraci Domenico
Published: July 2002

A clone (P2) coding for an allergen of Parietaria judaica (Pj) pollen has been isolated and sequenced from a cDNA library in lambda ZAP using a pool of 23 sera from Pj‐allergic patients. The clone contained an insert of 622 nucleotides with an open reading frame of 133 amino acids (aa) and a putative signal peptide of 31 aa giving a deduced mature processed protein of 102 aa with a molecular mass of 11 344 Da. The expressed recombinant protein, named rPar j 2.0101, was a major allergen since it reacted with IgE of 82% (23/28) of the sera of Pj‐allergic subjects analyzed. It was shown to be a new allergen since (i) the amino acid sequence homology with the already reported recombinant allergen Par j 1.0101 was 45% and (ii) there was no cross‐inhibition between rPar j 2.0101 and rPar j 1.0101. In addition, rPar j 2.0101 inhibited 35% of the specific IgE for 10–14 kDa native allergens and preincubation of sera from Pj‐allergic patients with both rPar j 2.0101 and rPar j 1.0101 fully abolished the IgE recognition of the 10–14 kDa native allergen region, suggesting that these two allergens contributed to the region.
Transcriptional regulatory regions for expression of the rat fatty acid synthase
Authors: Fukuda Hitomi , Iritani Nobuko , Noguchi Tamio
Published: July 2002

We previously mapped the sequences responsive to insulin/glucose stimulation and polyunsaturated fatty acid (PUFA) suppression in proximal promoter region from −57 to −35 of fatty acid synthase (FAS) gene of rat liver [Fukuda et al. (1996) Biochem. Mol. Biol. Int. 38, 987–996]. When two copies of the sequences spanning −57 to −35 were linked to a reporter gene containing heterologous promoter and were used for transfection, the reporter activity significantly increased in response to insulin/glucose treatment in hepetocytes. This increase was inhibited by addition of PUFA. Gel mobility shift assays using the sequence from −57 to −35 as a probe revealed nuclear factor(s) from rat liver that specifically complexed with the sequences. In addition, by antibody supershift assays, we have detected the binding of the transcriptional factor Sp1 at the GC‐rich region located within −57 to −35 of the FAS promoter. Cotransfection studies in rat hepatocytes, with the Sp1 expression vector and FAScat constructs, showed the inactivation of the promoter. These results were similar to those for the region from −68 to −52 of FAS gene (an insulin response element). The region from −68 to −52 of FAS gene competed for the formation of DNA–protein complexes to the region from −57 to −35 in the gel shift assay. Mutational analysis showed that the overlapping region of these two sequences was essential for the binding of Sp1. It has been demonstrated that both the regions from −57 to −35 and from −68 to −52 of the FAS gene are responsible for regulation due to insulin/glucose and PUFA, and Sp1 may be involved in the regulation.
Conversion of 2′,3′‐dideoxyadenosine (ddA) and 2′,3′‐didehydro‐2′,3′‐dideoxyadenosine (d4A) to their corresponding aryloxyphosphoramidate derivatives markedly potentiates their activity against human immunodeficiency virus and hepatitis B virus
Authors: Balzarini Jan , Kruining Johannes , Wedgwood Orson , Pannecouque Christophe , Aquaro Stefano , Perno Carlo-Federico , Naesens Lieve , Witvrouw Myriam , Heijtink Rudolf , De Clercq Erik , McGuigan Christopher
Published: July 2002

2′,3′‐Dideoxyadenosine (ddA), 2′,3′‐didehydro‐2′,3′‐dideoxyadenosine (d4A) and their lipophilic 5′‐monophosphate triester (aryloxyphosphoramidate) prodrugs were evaluated for their anti‐retrovirus and anti‐hepatitis B virus activity in various cell culture models. The aryloxyphosphoramidate derivatives of ddA (Cf 1093) and d4A (Cf 1001) showed markedly superior (100–1000‐fold) efficacies than the parent drugs against human immunodeficiency virus type 1 (HIV‐1), HIV‐2, simian immunodeficiency virus (SIV), Moloney murine sarcoma virus (MSV) and human hepatitis B virus (HBV) replication regardless of the cell type in which the virus replication was studied (i.e., human T‐lymphocyte CEM, MT‐4, Molt/4 and C8166 cells, peripheral blood lymphocytes (PBL), monocyte/macrophages (M/M), murine embryo fibroblasts and human hepatocyte cells). Also the selectivity index (ratio of cytotoxic concentration/antivirally effective concentration) of both aryloxyphosphoramidate prodrugs was markedly increased. In particular the d4A prodrug Cf 1001 showed a selectivity index of 300–3000 as compared with 2–3 for the parental d4A in established laboratory cell lines. Also Cf 1001 had a selectivity index of 400–650 in HIV‐1‐infected PBL and M/M, respectively. Both Cf 1001 and Cf 1093 were equally efficient as 3TC (lamivudine) in inhibiting HBV replication in hepatocytes, and rank among the most potent HIV and HBV inhibitors reported so far in cell culture.
Granulocytic differentiation of HL‐60 cells results in spontaneous apoptosis mediated by increased caspase expression
Authors: Watson R.William G , Rotstein Ori D , Parodo Jean , Bitar Richard , Hackam David , Marshall John C
Published: July 2002

HL‐60 cells differentiating into neutrophil‐like cells die an apoptotic death in vitro. Susceptibility to apoptosis is associated with decreased Bcl‐2 protein and mRNA expression; however, the effect of differentiation on the expression of pro‐apoptotic caspases is unknown. Spontaneous apoptosis occurred 6 days after retinoic acid treatment. Western blotting showed loss of Bcl‐2 by day 7, and new expression of ICE (caspase 1) and CPP32 (caspase 3) protein by day 2. Northern analysis demonstrated loss of Bcl‐2 mRNA and increases in ICE mRNA by day 2; CPP32 mRNA was unchanged. Differential Bcl‐2 and ICE mRNA expression was also found when granulocytic differentiation was stimulated by DMSO. Differentiated HL‐60 cell lysates exhibited functional ICE proteolytic activity. De novo caspase expression was responsible for the development of spontaneous apoptosis, since specific inhibitors of ICE (YVAD‐CMK) and CPP32 (DEVD‐CHO), inhibited retinoic acid induced spontaneous apoptosis. Functional maturation and susceptibility to apoptosis are both inducible and linked in this granulocyte precursor cell line.
HIV‐1 Nef protein‐induced apoptotic cytolysis of a broad spectrum of uninfected human blood cells independently of CD95(Fas)
Authors: Okada Harue , Takei Ryoichi , Tashiro Masato
Published: July 2002

The Nef protein of HIV‐1 binds to uninfected CD4+T lymphocytes and induces apoptotic cytolysis of the cells. We examined several human blood cell lines and peripheral blood mononuclear cells (PBMCs) for Nef‐induced apoptotic cell death. Soluble Nef protein was shown to bind to the cell surface of not only CD4+T cells but also CD8+T lymphocytes, B lymphocytes, macrophages and neutrophils. PBMCs from normal subjects resisted Nef binding, and activation of the cells with phytohemagglutinin or concanavalin A converted the cells to be susceptible to the binding. Cross‐linking of the Nef proteins bound to the cell surfaces with anti‐Nef antibody‐induced apoptotic cytolysis of the cells. The Nef‐mediated apoptosis occurred independently of CD95(Fas). These results suggest that soluble Nef protein, which is found in sera of HIV‐1 infected patients, is involved in the destruction of a broad spectrum of uninfected blood cells leading to immune suppression.
Constitutive neutrophil apoptosis in culture is modulated by cell density independently of β2 integrin‐mediated adhesion
Authors: Hannah Sharon , Nadra Imad , Dransfield Ian , Pryde James G. , Rossi Adriano G. , Haslett Christopher
Published: July 2002

Although inflammatory mediators modulate the rate of constitutive neutrophil apoptosis in vitro the effects of micro‐environmental conditions have not been fully investigated. In this study, we demonstrate that the rate of constitutive neutrophil apoptosis is affected by the number of cells per unit surface area, with enhanced survival at high cell density. Furthermore, the presence of protein or serum in the culture medium also enhances neutrophil survival. These effects were independent of β2 integrin‐mediated adhesion and were not influenced by specific adhesion to extracellular matrix components. Thus, the rate of neutrophil apoptosis is fundamentally influenced by micro‐environmental conditions and indicates that factors such as cell density and extracellular protein concentration must be considered when investigating mechanisms regulating inflammatory cell apoptosis in vitro.
MT1‐MMP on the cell surface causes focal degradation of gelatin films
Authors: d'Ortho Marie-Pia , Stanton Heather , Butler Michael , Atkinson Susan J , Murphy Gillian , Hembry Rosalind M
Published: July 2002

The membrane‐type matrix metalloproteinases (MT‐MMPs) are a subclass of the matrix metalloproteinase (MMP) family which uniquely possess a C‐terminal transmembrane domain and are initiators of an activation cascade for progelatinase A (MMP‐2). Recent studies have shown that they can also efficiently directly degrade a number of matrix macromolecules. We now show that cells expressing MT1‐MMP on their cell surfaces cause subjacent proteolysis of a gelatin film and that this proteolysis is inhibited by TIMP‐2 but not by TIMP‐1. These data indicate that expression of MT1‐MMP on the cell surface may lead to both progelatinase A activation and extracellular matrix degradation.
Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo
Authors: Tyler Beth M , McCormick Daniel J , Hoshall Clark V , Douglas Christopher L , Jansen Karen , Lacy Benjamin W , Cusack Bernadette , Richelson Elliott
Published: July 2002

Peptide nucleic acids (PNAs) are DNA analogs that can hybridize to complementary sequences with high affinity and stability. Here, we report the first evidence of intracellular delivery of PNAs in vivo. Two CNS receptors, an opioid (mu) and a neurotensin (NTR‐1), were targeted independently by repeated microinjection of PNAs into the periaqueductal gray. Behavioral responses to neurotensin (antinociception and hypothermia) and morphine (antinociception) were lost in a specific manner. Binding studies confirmed a large reduction in receptor sites. The loss of behavioral responses was long lasting but did fully recover. The implications of specifically and readily turning off gene expression in vivo are profound.
Study on the interactions between protein disulfide isomerase and target proteins, using immobilization on solid support
Authors: Muronetz Vladimir I , Zhang Nian Xian , Bulatnikov Igor G , Wang Chih-Chen
Published: July 2002

Interaction between protein disulfide isomerase, possessing not only isomerase but also chaperone‐like activity, and olygomeric enzyme, GAPDH, has been studied using technique of immobilization on insoluble support. PDI dimers bound to CNBr‐activated Sepharose were shown to posses high TPOR activity as well as the ability to reactivate lysozyme. Immobilized PDI was not found to interact neither with soluble tetrameric GAPDH, nor with soluble denatured GAPDH. However, soluble PDI binds effectively to immobilized GAPDH monomers; K
d was found to be 3.7×10−6 M, stoichiometry 0.824 mole PDI monomers per mole GAPDH monomers. Immobilized GAPDH tetramers do not interact with PDI. These observations are also confirmed by the data on electrophoresis of proteins bound to immobilized GAPDH monomers and tetramers. The ability of PDI to interact with denatured protein form, but not with the native one, is considered to be evidence of chaperone‐like activity of the enzyme.
The protein inhibitor of neuronal nitric oxide synthase (PIN): characterization of its action on pure nitric oxide synthases
Authors: Hemmens Benjamin , Woschitz Silvia , Pitters Eva , Klösch Burkhardt , Völker Christof , Schmidt Kurt , Mayer Bernd
Published: July 2002

Neuronal NO synthase (nNOS) was discovered recently to interact specifically with the protein PIN (protein inhibitor of nNOS) [Jaffrey, S.R. and Snyder, S.H. (1996) Science 274, 774–777]. We have studied the effects on pure NOS enzymes of the same GST‐tagged PIN used in the original paper. Unexpectedly, all NOS isoenzymes were inhibited. The IC50 for nNOS was 18±6 μM GST‐PIN with 63 nM nNOS after 30 min at 37°C. Uncoupled NADPH oxidation was inhibited similarly, whereas cytochrome c reductase activity, the K
M for l‐arginine, and dimerization were unaffected. We reconsider the physiological role of PIN in the light of these results.
α‐Tocopheryl succinate‐induced apoptosis in Jurkat T cells involves caspase‐3 activation, and both lysosomal and mitochondrial destabilisation
Authors: Neuzil Jiri , Svensson Irene , Weber Tobias , Weber Christian , Brunk Ulf T
Published: July 2002

α‐Tocopheryl succinate (α‐TOS), but not α‐tocopherol, triggered apoptosis in Jurkat T cells. Apoptosis was induced by α‐TOS in a time‐ and concentration‐dependent mode, and signs of apoptosis were visible at concentrations of α‐TOS as low as 30 μM, and within 3–5 h after addition of the ester. Employing a specific fluorogenic substrate, caspase‐3 was found to be activated rapidly in response to α‐TOS at 50 μM. We also found that Jurkat T cells challenged with α‐TOS, when exposed to the lysosomotropic weak base acridine orange, showed decreased lysosomal uptake of the dye. This is suggestive of the involvement of lysosomal destabilisation in apoptosis of the cells. Apoptosis of Jurkat T cells induced with α‐TOS also involved a drop in the mitochondrial membrane potential, although this phenomenon occurred after the initiation of lysosomal rupture. All apoptotic features observed with α‐TOS were very similar to those found when cross‐linking of the Fas receptor triggered apoptosis. These findings are consistent with the recent idea that vitamin E can contribute to elimination of malignant cells by the induction of apoptosis, and can be of (patho)physiological significance.
Major differences in oxysterol formation in human low density lipoproteins (LDLs) oxidized by OH/O2− free radicals or by copper
Authors: Zarev Stéphanie , Thérond Patrice , Bonnefont-Rousselot Dominique , Beaudeux Jean-Louis , Gardès-Albert Monique , Legrand Alain
Published: July 2002

The aim of our study was to determine the oxysterol formation in low density lipoproteins (LDLs) oxidized by defined oxygen free radicals (OH/O2

−). This was compared to the oxysterol produced upon the classical copper oxidation procedure. The results showed a markedly lower formation of oxysterols induced by OH/O2

− free radicals than by copper and thus suggested a poor ability of these radicals to initiate cholesterol oxidation in LDLs. Moreover, the molecular species of cholesteryl ester hydroperoxides produced by LDL copper oxidation seemed more labile than those formed upon OH/O2

−‐induced oxidation, probably due to their degradation by reaction with copper ions.
Identification of cytosolic aldehyde dehydrogenase 1 from non‐small cell lung carcinomas as a flavopiridol‐binding protein
Authors: Schnier Joachim B. , Kaur Gurmet , Kaiser Astrid , Stinson Sherman F. , Sausville Edward A. , Gardner John , Nishi Kayoko , Bradbury E.Morton , Senderowicz Adrian M.
Published: July 2002

The synthetic flavone flavopiridol can be cytostatic or cytotoxic to mammalian cells, depending on the concentration of the drug and the duration of exposure. It has been shown to inhibit the cyclin‐dependent kinase (CDK) family of cell cycle regulatory enzymes. However, the existence of additional potential targets for drug action remains a matter of interest to define. To identify cellular targets, flavopiridol was immobilized. CDKs, particularly CDK 4, bound weakly to immobilized flavopiridol when ATP was absent but not in its presence. Two proteins with molecular weights of 40 kDa and 120 kDa had high affinities to the immobilized flavopiridol independent of the presence of ATP. They were present in all cell lines analyzed: cervical (HeLa), prostate and non‐small cell lung carcinoma (NSCLC) cell lines. A 60‐kDa protein, which was present only in NSCLC cells and bound similarly well to immobilized flavopiridol, was identified as cytosolic aldehyde dehydrogenase class 1 (ALDH‐1). The level of this protein correlated with the resistance of NSCLC cell lines to cytotoxicity caused by 500 nM flavopiridol but not higher flavopiridol concentrations. Despite binding to ALDH‐1, there was no inhibition of dehydrogenase activity by flavopiridol concentrations as high as 20 μM and flavopiridol was not metabolized by ALDH‐1. The results suggest that high cellular levels of ALDH‐1 may reduce cytotoxicity of flavopiridol and contribute to relative resistance to the drug. This is the first report that flavopiridol binds to proteins other than CDKs.
One single mRNA encodes the centrosomal protein CCD41 and the endothelial cell protein C receptor (EPCR)
Authors: Rothbarth Karsten , Dabaghian A.Reza H , Stammer Hermann , Werner Dieter
Published: July 2002

The cDNA encoding the centrosomal protein CCD41 is identical with the cDNA for the endothelial cell protein C receptor. This finding is not due to an artefact, e.g. caused by selection of false positive clones. The segment of the CCD41 cDNA encoding the protein originally termed CCD41 and deletion mutants of it were fused with the nucleotide sequence encoding the enhanced green fluorescent protein (EGFP). Transfection and expression of the full length construct produces a fusion protein mainly located in cell membranes reflecting the receptor‐type protein. Deletion mutants, e.g. those where the signal sequence is deleted, result in fusion proteins which are exclusively incorporated into a small perinuclear structure which is the site of the centrosome. This result suggests that post‐translational modification, namely deletion of the signal sequence, is decisive for the centrosomal location of the resulting centrosomal protein while the unprocessed protein is incorporated into cell membranes.
Global trends in women's health
Authors: Fathalla M.F.
Published: July 2002

Global trends in women's health have to be looked at in the broader context of the definition of health as a state of complete physical, mental and social well‐being, and not merely the absence of disease or infirmity. Our species is undergoing a historical bio‐social evolution, with women positioned to have more power over their bodies and their lives. The implications for women's health are vast. Our profession has to face new challenges. The woman behind the mother is finally emerging, and making her presence felt. A reproductive evolution is sweeping the globe, with women having to lead a contraceptive life. A contraceptive technology revolution has benefited hundreds of millions, but the task is still unfinished. Demand for quality is substituting a desire for quantity in human reproduction. Sexual health is becoming an important psychosocial component of our health and well‐being. The mature adult woman and the elderly woman are rising to an important place in our health care. The widening bio‐social gap in adolescents dictates an increasing need for appropriate promotive, preventive and curative health care. One global trend in women's health unfortunately did not happen. Maternity is still, unnecessarily, a major cause of death and morbidity for women in developing countries.
Appropriate technology: antenatal care
Authors: Lumbiganon P.
Published: July 2002

Appropriate health technology should be effective, safe and feasible. The current antenatal care model originated from western countries. The absence of direct randomized, controlled trials precludes a straight forward evaluation of the impact of prenatal care on birth outcomes. Interventions of proven benefits in eliminating or alleviating adverse maternal outcomes include routine iron and folate supplementation in areas of high anemia prevalence, hemoglobin determination late in pregnancy, screening for asymptomatic bacteriuria by urine culture or dipstick, serologic screening and treatment of syphilis, obtaining a history of difficult labor in multipara or height in nullipara and external cephalic version at term. Interventions of proven benefits in eliminating or alleviating adverse newborn outcomes include routine measurement of fundal height, reduction of maternal physical strain, diagnosis and treatment of tuberculosis, malaria prophylaxis, adequate tetanus immunization, antenatal and perinatal Zidovudine in HIV‐positive mothers and one vaginal examination during pregnancy. Only these interventions of proven benefits should be implemented.
Locally delivered rhTGF‐β2 enhances bone ingrowth and bone regeneration at local and remote sites of skeletal injury
Authors: Sumner  , Turner T. M. , Urban R. M. , Leven R. M. , Hawkins M. , Nichols E. H. , McPherson J. M. , Galante J. O.
Published: July 2002

The purposes of the present study were to determine if recombinant human transforming growth factor‐beta‐2 (rhTGF‐β2) enhances bone ingrowth into porous‐coated implants and bone regeneration in gaps between the implant and surrounding host bone. The implants were placed bilaterally for four weeks in the proximal humeri of skeletally mature, adult male dogs in the presence of a 3‐mm gap. In three treatment groups of animals, the test implant was treated with hydroxyapatite/tricalcium phosphate (HA/TCP) and rhTGF‐β2 in buffer at a dose per implant of 1.2 μg (n = 6), 12 μg (n = 7), or 120 μg (n = 7) and placed in the left humerus. In these same animals, an internal control implant treated only with HA/TCP and buffer was placed in the right humerus. In a non‐TGF‐β treated external control group of animals (n = 7), one implant was treated with HA/TCP while the contralateral implant was not treated with the ceramic. In vitro analyses showed that approximately 15% of the applied dose was released within 120 h with most of the release occurring in the first 24 h. The TGF‐μ treated implants had significantly more bone ingrowth than the controls with the greatest effect in the 12 μg/implant group (a 2.2‐fold increase over the paired internal control (P = 0.004) and a 4‐fold increase over the external control (P < 0.001)). The TGF‐β treated implants had significantly more bone formation in the gap than the controls with the greatest effect in the 12 and 120 μg groups (1.8‐fold increases over the paired internal controls (P = 0.003 and P = 0.012, respectively) and 2.8‐fold increases over the external controls (P < 0.001 and P = 0.001, respectively)). Compared to the external controls, the internal control implants tended to have more bone ingrowth (1.9‐fold increase, P = 0.066) and had significantly more bone formation in the gap (1.7‐fold increase, P = 0.008). Thus, application of rhTGF‐β2 to a porous‐coated implant‐stimulated local bone ingrowth and gap healing in a weakly dose‐dependent manner and stimulated bone regeneration in the 3‐mm gap surrounding the contralateral control implant, a site remote from the local treatment with the growth factor. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Nerve growth factor modulates myelin‐associatedglycoprotein binding to sensory neurons
Authors: Turnley Ann M. , Bartlett Perry F.
Published: July 2002

Myelin‐associated glycoprotein (MAG) is a molecule expressed by myelinating cells atthe myelin:axon interface, which binds to an as yet unidentified molecule on neurons. We haveused a MAG‐immunoglobulin Fc fusion protein to examine the expression and regulation of theMAG binding molecule on sensory neurons in culture. Binding of the MAG‐Fc reached amaximum at 24‐48 h and was higher on neurons which expressed high levels of neurofilament.Nerve growth factor (NGF) upregulated expression of the MAG binding molecule in a dosedependent manner. Schwann cells co‐cultured with sensory neurons in serum‐free mediumstimulated maximal expression of the MAG binding molecule, which was decreased by addition ofanti‐NGF to the co‐cultures. This indicated that Schwann cells can modulate expression of theMAG binding molecule via production of NGF and may represent a physiological mechanism forregulation of MAG MAG binding molecule interactions during myelination and remyelination. 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved
Psychopathology of alcoholics during withdrawal and early abstinence
Authors: Wetterling T , Junghanns K
Published: July 2002

Epidemiologic surveys show a high lifetime co-morbidity with psychiatric disorders (e.g., depression and anxiety) in alcoholics. However, alcoholics frequently complained about psychopathologic symptoms, particularly during alcohol withdrawal. There is some evidence that symptomatology decreases spontaneously with prolonged abstinence. Thus, the question arises whether high levels of psychopathology could be accounted for by withdrawal effects. This study was aimed at examining the impact of the alcohol withdrawal severity (assessed by the AWS scale) on psychopathologic symptoms. The psychopathologic profile of 110 alcoholics as measured by the Symptom Checklist-90 revised (SCL-90-R) was compared to that of 253 patients with adjustment, anxiety or depressive disorders (according to ICD-10 criteria). No relationship between the severity of alcohol withdrawal and psychopathology could be found which might hint at two different neurobiological processes underlying these phenomena. The comparison with patients suffering from depression or anxiety disorders revealed that the global symptom severity of alcoholics undergoing withdrawal was similar, but recovery was achieved more rapidly than in the other groups. On the other hand, the self-rated psychopathologic symptom profile of alcoholics was rather similar to that of patients with adjustment disorders. While about one-quarter of the alcoholics reported severe psychopathology on admission, only about 10% showed symptomatology at discharge about three weeks later, predominantly depression or anxiety. These results underline the notion that much of the psychopathology described by alcoholics decreases within 2–3 weeks after withdrawal without specific treatment.
Meta-analytic study of the benefits and risks of treating chronic schizophrenia with risperidone or conventional neuroleptics
Authors: Bech P , Peuskens JCJR , Marder SR , Chouinard G , Høyberg OJ , Huttunen MO , Blin O , Claus A
Published: July 2002

Data from six randomised, controlled, comparative studies of risperidone and conventional neuroleptics (haloperidol, zuclopenthixol and perphenazine) in the treatment of 911 patients with chronic schizophrenia were analysed to estimate the benefits and risks of treatment. Efficacy and risk of treatment were assessed by means of the Positive and Negative Syndrome Scale (PANSS) and the Extrapyramidal Symptom Rating Scale (ESRS). An effect size (difference between treatments) was calculated from the PANSS and ESRS scores. The effect size of antipsychotic effect favoured risperidone (sizes ranged from 0.22 to 0.37 on the PANSS subscales), and the effect size of safety also favoured risperidone (sizes ranged from 0.18 to 0.36 on the ESRS). An analysis of the proportions of patients requiring antiparkinsonian medication produced an effect size of 0.37 (20% of risperidone patients and 38% of patients receiving a conventional neuroleptic required antiparkinsonian medication). These data indicate that risperidone is a more effective antipsychotic than the conventional agents and causes less severe extrapyramidal symptoms.
Change in Maternal Concerns During the 6 Weeks Postpartum Period: A Study of Primiparous Mothers in Dar es Salaam, Tanzania
Authors: Lugina Helen I. , Christensson Kyllike , Massawe Siriel , Nystrom Lennarth , Lindmark Gunilla
Published: July 2002

The purpose of this study was to describe the postpartum concerns of primiparas. A cohort study included 79 mothers in Dar es Salaam, Tanzania. Mothers sorted topics into worry, interest, and confidence. Trends of decreasing worry and increasing interest and confidence for baby‐related and mother‐related topics were observed from 1 to 6 weeks. At 1 week mothers worried about baby's eyes, respiration, temperature, safety, and crying; but, at 6 weeks only crying was a problem. Need for information was constant about general health, baby behavior, and care of the baby. At 1 week mothers worried about swollen perineum, and feeling tired and nervous. They wanted information about preventing hemorrhage and infection and taking care of the perineum, breasts, and nipples. Trends of increasing worry and decreasing confidence were observed with respect to family relationships. At 6 weeks, mothers worried about the husband/partner's reaction to themselves and to the baby. Confidence in relatives' reaction to themselves and the baby decreased. Being aware of the changes in the way concerns are expressed may guide nursing/midwifery interventions for mothers as to the content and timing.
A novel quality assurance procedure for trajectory log validation using phantom‐less real‐time latency corrected EPID images
Authors: Lim Seng Boh , Zwan Benjamin J. , Lee Danny , Greer Peter B. , Lovelock Dale Michael
Published: February 2021

The use of trajectory log files for routine patient quality assurance is gaining acceptance. Such use requires the validation of the trajectory log itself. However, the accurate localization of a multileaf collimator (MLC) leaf while it is in motion remains a challenging task. We propose an efficient phantom‐less technique using the EPID to verify the dynamic MLC positions with high accuracy. Measurements were made on four Varian TrueBeams equipped with M120 MLCs. Two machines were equipped with the S1000 EPID; two were equipped with the S1200 EPID. All EPIDs were geometrically corrected prior to measurements. Dosimetry mode EPID measurements were captured by a frame grabber card directly linked to the linac. All leaf position measurements were corrected both temporally and geometrically. The readout latency of each panel, as a function of pixel row, was determined using a 40 × 1.0 cm2 sliding window (SW) field moving at 2.5 cm/s orthogonal to the row readout direction. The latency of each panel type was determined by averaging the results of two panels of the same type. Geometric correction was achieved by computing leaf positions with respect to the projected isocenter position as a function of gantry angle. This was determined by averaging the central axis position of fields at two collimator positions of 90° and 270°. The radiological to physical leaf end position was determined by comparison of the measured gap with that determined using a feeler gauge. The radiological to physical leaf position difference was found to be 0.1 mm. With geometric and latency correction, the proposed method was found to be improve the ability to detect dynamic MLC positions from 1.0 to 0.2 mm for all leaves. Latency and panel residual geometric error correction improve EPID‐based MLC position measurement. These improvements provide for the first time a trajectory log QA procedure.
Dosimetric evaluation of skin collimation with tungsten rubber for electron radiotherapy: A Monte Carlo study
Authors: Wakabayashi Kazuki , Monzen Hajime , Tamura Mikoto , Matsumoto Kenji , Takei Yoshiki , Nishimura Yasumasa
Published: February 2021

Purpose

Skin collimation provides a sharp penumbra for electron beams, while the effect of bremsstrahlung from shielding materials is a concern. This phantom study was conducted to evaluate the safety and efficacy of a real‐time variable shape rubber containing‐tungsten (STR) that can be placed on a patient’s skin.

Methods

Electron beam profiles were acquired with the STR placed on a water‐equivalent phantom and low melting‐point alloy (LMA) placed at the applicator according to commonly used procedures (field sizes: 20‐ and 40‐mm diameters). Depth and lateral dose profiles for 6‐ and 12‐MeV electron beams were obtained by Monte Carlo (MC) simulations and were benchmarked against film measurements. The width of the off‐axis distance between 80% and 20% doses (P80‐20) and the maximum dose were obtained from the lateral dose profiles. Bremsstrahlung emission was analyzed by MC simulations at the depth of maximum dose (R100).

Results

The depth dose profiles calculated by the MC simulations were consistently within 2% of the measurements. The P80‐20 at R100 for 20‐ and 40‐mm diameters were 4.0 mm vs. 7.6 mm (STR vs. LMA) and 4.5 mm vs. 9.2 mm, respectively, for the 6‐MeV electron beam with 7.0‐mm‐thick STR, and 2.7 mm vs. 5.6 mm and 4.5 mm vs. 7.1 mm, respectively, for the 12‐MeV electron beam with 12.0‐mm‐thick STR. A hotspot was not observed on the lateral dose profiles obtained with the STR at R100. The bremsstrahlung emission under the region shielded by the STR was comparable to that obtained with the LMA, even though the STR was placed on the surface of the phantom.

Conclusions

Skin collimator with STR provided superior dosimetric characteristics and comparable bremsstrahlung emission to LMA collimator at the applicator. STR could be a new tool for the safe and efficient delivery of electron radiotherapy.
Bioinspired Conductive Silk Microfiber Integrated Bioelectronic for Diagnosis and Wound Healing in Diabetes
Authors: Jia Zhanrong , Gong Jinglei , Zeng Yan , Ran Jinhui , Liu Jin , Wang Kefeng , Xie Chaoming , Lu Xiong , Wang Jun
Published: February 2021

Ideal epidermal bioelectronics can be used not only for long‐term detection of physiological signals for disease diagnosis but also for chronic disease treatment. Silk, an animal‐derived fiber with good biocompatibility and skin‐affinity, is widely used in flexible bioelectronics. However, silk fibers are insulating. In this study, ultralong conductive silk microfibers (mSFs) are fabricated by extracting mSF from raw silk using a bioinspired extraction‐protection process with the assistance of polydopamine, followed by deposition of poly(3,4‐ethylenedioxythiophene) (PEDOT) on its surface. The conductive mSFs are produced and used to fabricate a conductive flexible silk fibroin patch, which is used as a conformable bioelectronic for monitoring physiological signals. In addition, as the conductive mSF possessed anti‐oxidative activity, the patch exhibits excellent performance in chronic diabetic wound healing by reducing inflammation and regulating oxidative stress. Thus, this bioinspired strategy produces conductive silk fibers that can be used as biocompatible building blocks, opening new avenues for employing passive silk as an active component in the design of epidermal wound repair biomaterials and next‐generation flexible epidermal bioelectronics.
Mimicking Nature's Butterflies: Electrochromic Devices with Dual‐Sided Differential Colorations
Authors: Chen Jian , Wang Zhen , Liu Chenglong , Chen Zhigang , Tang Xueqing , Wu Qi , Zhang Shu , Song Ge , Cong Shan , Chen Qin , Zhao Zhigang
Published: February 2021

Some butterfly species such as the orange oakleaf (Kallima inachus) have strikingly different colors on the dorsal (front) sides of their wings compared to those on the ventral (back) sides of their wings, which helps camouflage the butterflies from predators and attract potential mates. However, few human‐made materials, devices, and technologies can mimic such differential coloring for a long time. Here, a new type of Janus‐structured two‐sided electrochromic device is developed that, upon application of different voltages, exhibits a coloration state on one side that is distinctly different from that on the other side. This is achieved by inserting an optically thin (4–8 nm) metallic layer with a complex refractive index, such as a layer composed of tungsten, titanium, copper or silver, into typical electrochromic structures.
Water–Salt Oligomers Enable Supersoluble Electrolytes for High‐Performance Aqueous Batteries
Authors: Cai Shengying , Chu Xingyuan , Liu Chang , Lai Haiwen , Chen Hao , Jiang Yanqiu , Guo Fan , Xu Zhikang , Wang Chunsheng , Gao Chao
Published: February 2021

Aqueous rechargeable batteries are highly safe, low‐cost, and environmentally friendly, but restricted by low energy density. One of the most efficient solutions is to improve the concentration of the aqueous electrolytes. However, each salt is limited by its physical solubility, generally below 21–32 mol kg−1 (m). Here, a ZnCl2/ZnBr2/Zn(OAc)2 aqueous electrolyte with a record super‐solubility up to 75 m is reported, which breaks through the physical solubility limit. This is attributed to the formation of acetate‐capped water–salt oligomers bridged by Br−/Cl−‐H and Br−/Cl−/O‐Zn2+ interactions. Mass spectrometry indicates that acetate anions containing nonpolarized protons prohibit the overgrowth and precipitation of ionic oligomers. The polymer‐like glass transition temperature of such inorganic electrolytes is found at ≈−70 to −60 °C, without the observation of peaks for salt‐crystallization and water‐freezing from 40 to −80 °C. This supersoluble electrolyte enables high‐performance aqueous dual‐ion batteries that exhibit a reversible capacity of 605.7 mAh g−1, corresponding to an energy density of 908.5 Wh kg−1, with a coulombic efficiency of 98.07%. In situ X‐ray diffraction and Raman technologies reveal that such high ionic concentrations of the supersoluble electrolyte enable a stage‐1 intercalation of bromine into macroscopically assembled graphene cathode.
Base‐Promoted Synthesis of Polysubstituted 4‐Aminoquinolines from Ynones and 2‐Aminobenzonitriles under Transition‐Metal‐Free Conditions
Authors: Kumar Ankit , Mishra Pawan K. , Saini Kapil Mohan , Verma Akhilesh K.
Published: February 2021

A transition‐metal‐free and base‐promoted one‐pot reaction of ynones with 2‐aminobenzonitriles is described. The reaction was initiated through sequential aza‐Michael addition/intramolecular annulation to afford various multisubstituted 4‐aminoquinolines and 4‐amino‐1,8‐naphthyridines in good to excellent yields. Operational simplicity, high atom‐economy with broad substrate scope makes this protocol more attractive. Also, the gram‐scale synthesis and further transformation of the product were studied. Additionally, 2‐haloarylyones as substrate provide N‐arylquinolones as the sole product via the SNAr mechanism.

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Super High‐Expansion Poly(Lactic Acid) Foams with Excellent Oil‐Adsorption and Thermal‐Insulation Properties Fabricated by Supercritical CO2 Foaming
Authors: Li Bo , Zhao Guoqun , Wang Guilong , Zhang Lei , Gong Jie , Shi Zhanlin
Published: February 2021

Bio‐based and biodegradable poly(lactic acid) (PLA) foams with a high expansion ratio show great application potential in oil‐adsorption and thermal‐insulation, which are crucial for oil‐spill cleanup and energy saving. However, it is difficult to prepare high‐expansion PLA foam due to the poor melt strength and complex crystallization behavior of PLA. Herein, super high‐expansion PLA foams with excellent oil‐adsorption and thermal‐insulation properties are successfully prepared using a modified supercritical CO2 foaming technology without introducing eco‐unfriendly chain extenders or fillers. High‐strength melt at low temperature and low‐strength melt at high temperature are used to prepare closed‐cell and open‐cell foams, respectively. The resulting PLA closed‐cell foam with an expansion ratio of 60 shows a thermal conductivity as low as 31.7 mW m−1 k−1, and the PLA open‐cell foam with an expansion ratio of 43 and exhibits an adsorption capacity of 10.9–31.2 g g−1 for various oils. Based on the prepared PLA foams with tunable structure, the influence of cell structure on the properties of the foam is also studied. Of particular note, reducing the cell size can obviously enhance the surface hydrophobicity of PLA foam. This work provides a green strategy for the preparation of eco‐friendly materials applied in environment protection and energy conservation.
Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions
Authors: Chang Chun‐Wei , Lin Mei‐Huei , Chan Chieh‐Kai , Su Kuan‐Yu , Wu Chia‐Hui , Lo Wei‐Chih , Lam Sarah , Cheng Yu‐Ting , Liao Pin‐Hsuan , Wong Chi‐Huey , Wang Cheng‐Chung
Published: February 2021

The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well‐defined reactivity and promoters were organized and processed by the designed software program “GlycoComputer” for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated.
Conductive Metallophthalocyanine Framework Films with High Carrier Mobility as Efficient Chemiresistors
Authors: Yue Yan , Cai Peiyu , Xu Xiaoyi , Li Hanying , Chen Hongzheng , Zhou Hong‐Cai , Huang Ning
Published: February 2021

The poor electrical conductivity of two‐dimensional (2D) crystalline frameworks greatly limits their utilization in optoelectronics and sensor technology. Herein, we describe a conductive metallophthalocyanine‐based NiPc‐CoTAA framework with cobalt(II) tetraaza[14]annulene linkages. The high conjugation across the whole network combined with densely stacked metallophthalocyanine units endows this material with high electrical conductivity, which can be greatly enhanced by doping with iodine. The NiPc‐CoTAA framework was also fabricated as thin films with different thicknesses from 100 to 1000 nm by the steam‐assisted conversion method. These films enabled the detection of low‐concentration gases and exhibited remarkable sensitivity and stability. This study indicates the enormous potential of metallophthalocyanine‐based conductive frameworks in advanced stand‐off chemical sensors and provides a general strategy through tailor‐make molecular design to develop sensitive and stable chemical sensors for the detection of low‐concentration gases.
Unravelling the Structure of a Medium‐Sized Metalloid Gold Nanocluster and its Filming Property
Authors: Gu Wanmiao , Zhao Yan , Zhuang Shengli , Zha Jun , Dong Jingwu , You Qing , Gan Zibao , Xia Nan , Li Jin , Deng Haiteng , Wu Zhikun
Published: February 2021

Unravelling the structure of thiolated metalloid gold nanoclusters in the medium‐sized range by single crystal X‐ray crystallography (SCXC) is challenging. Herein, we successfully synthesized a novel Au67(SR)35 nanocluster, and unravelled its single crystal structure by SCXC, which features a mix‐structured Au48 kernel protected by one Au4(SR)5 staple and fifteen Au(SR)2 staples. Unprecedentedly, this structure can be thermally induced to aggregate into larger nanoparticles and self‐deposit to form a gold nanoparticles film onto the walls of a vial or other substrates such as quartz, mica or ceramic, which can be developed into a facile, substrate‐universal and scalable filming method. The film exhibits high sensitivity, uniformity and recyclability as a surface‐enhanced Raman scattering (SERS) substrate and can be applied for detecting multiple organic pollutants.