bluuebunny/crossref_metadata_2025 huggingface dataset:
Adapting and Evaluating Implementation of a Tobacco-Free Workplace Program in Behavioral Health Centers
Authors: Leal Isabel Martinez , Chen Tzu-An , Correa-Fernández Virmarie , Le Kathy , O'Connor Daniel P. , Kyburz Bryce , Wilson William T. , Williams Teresa , Reitzel Lorraine R.
Published: October 2020

Objectives: State-administered community behavioral health centers (CBHCs) rarely treat tobacco dependence, despite high client tobacco use. Using a mixed-methods approach we examine the adaptation and implementation of an evidence-based tobacco-free workplace (TFW) program in
2 CBHCs (17 individual clinics). Methods: Varied data collection included pre- and post-implementation leader, clinician, and staff surveys; pre-, mid-, and post-implementation staff and client focus groups; and monthly implementation logs. The RE-AIM framework guided translation of
behavioral interventions into sustainable practice. Results: Pre- to post-implementation increases were seen in training receipt among clinicians and employees. Both CBHCs adopted a 100% TFW policy, integrated tobacco screenings into routine practice, and delivered evidence-based practices
(EBPs). Qualitative methods enlisted key stakeholders contributing towards adapting program strategies to local contexts, addressing barriers, adjusting tobacco screening administration, and understanding reasons for success or failure to implement specific components. Conclusions:
Program implementation at both CBHCs increased organizational capacity in the provision of EBPs to treat tobacco dependence through successfully meeting the majority of our RE-AIM targets. Findings contribute to the development of flexible strategies and interventions responsive to variable
implementation contexts and barriers; enhancing the effectiveness and sustainability of a TFW program.
African-American Views of Food Choices and Use of Traditional Foods
Authors: Winham Donna M. , Knoblauch Simon T. , Heer Michelle M. , Thompson Sharon V. , Der Ananian Cheryl
Published: October 2020

Objectives: In this study, we describe dietary intakes and examine variation among African-American adults in the Southwest, and identify barriers to engaging in healthy dietary behaviors, and use of traditional African-American foods, including pulses. Methods: Using
mixed-methods parallel analysis, 97 African Americans aged 25-60 years completed surveys on lifestyle and dietary habits prior to focus group discussions in 3 geographic regions of Arizona. We identified themes in the qualitative transcripts using an inductive approach informed by Grounded
Theory. Survey data were compared by sex, and age cohort via chi-square and ANOVA. Results: Qualitative knowledge of healthy choices was high for most participants, but survey dietary in-takes were below recommendations for fruit, vegetables, fiber, and pulses. Greens, fried chicken
and fish, barbequed meats, okra-corn-tomato mix, grits, and sweet potatoes were eaten at least twice a month by 30%-50%. Statistically significant food consumption differences were observed by sex, age, and income. Healthy eating barriers included cost, access, convenience or time to prepare,
accessibility, and cultural preferences and traditions. Interest in food preparation education was a common theme. Conclusions: Arizona African Americans retain elements of traditional foods in their diet. Health education should offer practical solutions for the cited barriers, be
culturally relevant, and build on existing knowledge.
Kronik
Authors: Philipson Lotte
Published: October 2020

Indhold: Grundstensnedlæggelse; 7. oktober 1996 blev grundstenen lagt i "Den sorte Diamant" på Havnefronten; I Hendes Majestæt Dronning Margrethe den Andens femogtyvende regeringsår den syvende oktober 1996 blev grundstenen til "Den sorte Diamant", Det kongelige Biblioteks udbygning på Hav­nefronten, nedlagt på dette seed af Kultur­minister Jytte Hilden, som indmurede den første sten, Overborgmester Jens Kramer Mikkelsen, som indmurede den anden sten, og Direktør Erland Kolding Nielsen, der som bibliotekets repræsentant ind­murede den tredie sten; Schmidt, Hammer & Lassen; Rejsegilde på Amager 4. oktober 1996; På Dee kongelige Biblioteks magasin­byggeri på Amager blev der afholdt rejsegilde 4. oktober 1996; Forum bogmesse 15.-17. november; Besøg; Erhvervelser; Personalia; Udlån til udstillinger;
Kronik
Authors: Philipson Lotte
Published: October 2020

Indhold: Den 26. juni 1998 kunne Det Kongelige Bibliotek overtage etape 1 af Dissing og Weitlings biblioteksbygning beliggende Njalsgade 112 på Amager som nabo til Københavns Universitet; Adgangsforhold; Fordelingsrum; Lukkede Magasiner; Erhvervelser; Besøg; Personalia;
Kronik
Authors: Leergaard Joan
Published: October 2020

Indhold: Brug af Det Kongelige Bibliotek slår rekord; Bevaring af internettet; Webtidsmaskine som bryllupsgave; Det Kongelige Biblioteks og Statsbiblioteket i Århus1 gave i forbindelse med kronprins Frederik og Mary Donaldsons bryllup 14. maj er en webtidsmaskine; IT-udstyr til synshandikappede; Nye baser i Elektra; Fund og Forskning på nettet; Retroprojekter gør REX mere komplet; David Simonsens arkiv gjort tilgængeligt efter 70 år; REX — nyt design, nye muligheder, ny adresse; H.C. Andersens Almanakker online; Trykte kataloger på nettet; Harpestrængs urtebog på nette; Nyt i Den nationale Billedbase; Dansk Kortfortegnelse 2003 er udkommet; Engelske noder fra 1820-40 på nettet; Golden Days i Diamanten; Foredrag; Debat; Kulturarven i den digitale tidsalder; Udstillinger; Musikarrangementer;
Kronik og Publikationer
Authors: Philipson Lotte
Published: October 2020

Indhold: Bøger og bibliotek; Det Kongelige Bibliotek på nettet; Digitaliserede noder - nu også i særlig REX-base; Udstillinger; Foredrag; Foredragsrækken: Profiler i dansk besættelsestidshistorie; Musikarrangementer; Kulturnatten; Bogseminar; Erhvervelser; Udlån til udstillinger; Publikationer;
Kronik og publikationer
Authors: Philipson Lotte
Published: October 2020

Indhold: Bøger og bibliotek; Universitetsbiblioteker har deres skæbne - reportage fra KUBIS morgenmøde;  Få bogen vi e-mail; Det Kongelige Biblotek på nettet; Per Højholt og Gitte-monologerne live; Udstillinger; Foredragsrækken Frigørelsens århundrede; Foredrag og debat; Musik, Erhvervelser; Publikationer
Kronik
Authors: Philipson Lotte
Published: October 2020

Indhold: Forfatteren Asger Jorn; Det kongelige Bibliotek har på Museum Tusculanums Forlag udgivet; Bøger i Forum; Forhallens ottekantede montre; Samfundsvidenskabeligt nærbibliotek i Fiolstræde; I henhold til indstillingerne fra Det kongelige Biblioteks ModerniseringsprojektsArbejdsgruppe 2 i 1988 (se rapporten: Bibliotek og Universitet.Kbh., 1988, kapitel 7) skal Universitetsbiblioteket i Fiolstræde omdannes til nærbibliotek for samfundsvidenskaberne: jura, statskundskab, sociologi og økonomi; Bogseminar 1992; Erhvervelser; Udlån til udstillinger; Besøg; Personalia;
Kronik
Authors: Philipson Lotte
Published: October 2020

Rued Langgaard 100 år; Europæiske Bogbind '93 • European Bookbindings '93; Beskyt og Bevar / Nye Danske Bogbind; 'Den ottekantede'; Fiolstræde; Havnefronten; Udlån til udstillinger; Besøg; Andre meddelelser; Andre meddelelser; Personalia;
ARID1A loss in adult hepatocytes activates β-catenin-mediated erythropoietin transcription
Authors: Riou Rozenn , Ladli Meriem , Gerbal-Chaloin Sabine , Bossard Pascale , Gougelet Angélique , Godard Cécile , Loesch Robin , Lagoutte Isabelle , Lager Franck , Calderaro Julien , Dos Santos Alexandre , Wang Zhong , Verdier Frédérique , Colnot Sabine
Published: October 2020

Erythropoietin (EPO) is a key regulator of erythropoiesis. The embryonic liver is the main site of erythropoietin synthesis, after which the kidney takes over. The adult liver retains the ability to express EPO, and we discovered here new players of this transcription, distinct from the classical hypoxia-inducible factor pathway. In mice, genetically invalidated in hepatocytes for the chromatin remodeler Arid1a, and for Apc, the major silencer of Wnt pathway, chromatin was more accessible and histone marks turned into active ones at the Epo downstream enhancer. Activating β-catenin signaling increased binding of Tcf4/β-catenin complex and upregulated its enhancer function. The loss of Arid1a together with β-catenin signaling, resulted in cell-autonomous EPO transcription in mouse and human hepatocytes. In mice with Apc-Arid1a gene invalidations in single hepatocytes, Epo de novo synthesis led to its secretion, to splenic erythropoiesis and to dramatic erythrocytosis. Thus, we identified new hepatic EPO regulation mechanism stimulating erythropoiesis.
Structural and functional characterization of G protein–coupled receptors with deep mutational scanning
Authors: Jones Eric M , Lubock Nathan B , Venkatakrishnan AJ , Wang Jeffrey , Tseng Alex M , Paggi Joseph M , Latorraca Naomi R , Cancilla Daniel , Satyadi Megan , Davis Jessica E , Babu M Madan , Dror Ron O , Kosuri Sriram
Published: October 2020

The >800 human G protein–coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state- and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here, we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G protein signal transduction. We tested 7800 of 7828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β2AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β2AR signaling, mutations in the human population that are potentially loss of function, and residues that modulate basal activity. Using unsupervised learning, we identify residues critical for signaling, including all major structural motifs and molecular interfaces. We also find a previously uncharacterized structural latch spanning the first two extracellular loops that is highly conserved across Class A GPCRs and is conformationally rigid in both the inactive and active states of the receptor. More broadly, by linking deep mutational scanning with engineered transcriptional reporters, we establish a generalizable method for exploring pharmacogenomics, structure and function across broad classes of drug receptors.
An interactive meta-analysis of MRI biomarkers of myelin
Authors: Mancini Matteo , Karakuzu Agah , Cohen-Adad Julien , Cercignani Mara , Nichols Thomas E , Stikov Nikola
Published: October 2020

Several MRI measures have been proposed as in vivo biomarkers of myelin, each with applications ranging from plasticity to pathology. Despite the availability of these myelin-sensitive modalities, specificity and sensitivity have been a matter of discussion. Debate about which MRI measure is the most suitable for quantifying myelin is still ongoing. In this study, we performed a systematic review of published quantitative validation studies to clarify how different these measures are when compared to the underlying histology. We analyzed the results from 43 studies applying meta-analysis tools, controlling for study sample size and using interactive visualization (https://neurolibre.github.io/myelin-meta-analysis). We report the overall estimates and the prediction intervals for the coefficient of determination and find that MT and relaxometry-based measures exhibit the highest correlations with myelin content. We also show which measures are, and which measures are not statistically different regarding their relationship with histology.
Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus
Authors: Rattner Amir , Terrillion Chantelle E , Jou Claudia , Kleven Tina , Hu Shun Felix , Williams John , Hou Zhipeng , Aggarwal Manisha , Mori Susumu , Shin Gloria , Goff Loyal A , Witter Menno P , Pletnikov Mikhail , Fenton André A , Nathans Jeremy
Published: October 2020

In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to eliminatingWntless(Wls) in a subset of cortical progenitors withGfap-Cre. Other cells in theWlsfl/-;Gfap-Crehippocampus were minimally affected, as determined by single nucleus RNA sequencing. CA3 pyramidal cells, the targets of DGC-derived mossy fibers, exhibited normal morphologies with a small reduction in the numbers of synaptic spines.Wlsfl/-;Gfap-Cremice have a modest performance decrement in several complex spatial tasks, including active place avoidance. They were also modestly impaired in one simpler spatial task, finding a visible platform in the Morris water maze. These experiments support a role for DGCs in enhancing spatial learning and memory.
CUDA-Based Particle Swarm Optimization in Reflectarray Antenna Synthesis
Authors: Capozzoli A. , Curcio C. , Liseno A.
Published: October 2020

We show how reflectarray antenna synthesis can take profit from parallel computing on Graphics Processing Units (GPUs). The presented approach uses an implementation of Particle Swarm Optimization in CUDA language and accelerates the computation of the field radiated by the reflectarray using a GPU- mplemented Non-Uniform FFT routine. Numerical results show how computing time can be kept convenient for the application at hand.
Immunoglobulin superfamily member 10 is a novel prognostic biomarker for breast cancer
Authors: Wang Mengxue , Dai Meng , Wu Yu-shen , Yi Ziying , Li Yunhai , Ren Guosheng
Published: October 2020

Background

Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear.

Method

By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA).

Results

According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR) = 1.793, 95% confidence interval (CI) [1.141–2.815], P = 0.011) and RFS (HR = 2.298, 95% CI [1.317–4.010], P = 0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways.

Conclusions

This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.
The phosphatidic acid phosphatase of the chloroplast envelope is located on the inner envelope membrane
Authors: Block Maryse A. , Dorne Albert-Jean , Joyard Jacques , Douce Roland
Published: July 2002

The envelope from spinach chloroplasts contains an alkaline phosphatidic acid phosphatase which was found to be located on the inner envelope membrane. The diacylglycerol formed by this enzyme from endogenous phosphatidic acid is then used as a substrate for galactolipid synthesis on the inner envelope membrane.
In vitro biosynthesis of the human cell surface receptor for transferrin
Authors: Schneider C. , Asser U. , Sutherland D.R. , Greaves M.F.
Published: July 2002

The human cell surface receptor for transferrin is a transmembrane phosphoglycoprotein composed of two disulphide linked and apparently identical subunits of M
r 90 000. Using an affinity purified, polyclonal rabbit antibody, we have studied the in vitro biosynthesis of this receptor. The primary translation product, synthesised in a rabbit reticulocyte lysate programmed with human placental RNA, appears to have the same M
r (78 000) as the unglycosylated molecule immunoprecipitated from tunicamycin‐treated cells. In the presence of a dog pancreatic microsomal system the cell free system accurately reproduces the glycosylation and the asymmetric transmembrane integration
Lectin‐like binding of Bacillus thuringiensis var, kurstaki lepidopteran‐specific toxin is an initial step in insecticidal action
Authors: Knowles B.H. , Thomas W.E. , Ellar D.J.
Published: July 2002

The two δ‐endotoxins comprising the Bacillus thuringiensis var. kurstaki HD1 insecticidal protein crystal were separated. The lepidopteran‐specific protoxin was activated in vitro and its mechanism of action investigated. Toxicity towards Choristoneura fumiferana CF1 cells was specifically inhibited by preincubation of the toxin with N‐acetylgalactosamine and N‐acetylneuraminic acid. The lectins soybean agglutinin and wheat germ agglutinin, which bind N‐acetylgalactosamine, also inhibited toxicity. Since N‐acetylneuraminic acid is not known to occur in insects, these results suggest that the toxin may recognise a specific plasma membrane glycoconjugate receptor with a terminal N‐acetylgalactosamine residue.
Regulation of insulin secretion by cAMP in rat islets of Langerhans permeabilised by high‐voltage discharge
Authors: Jones Peter M. , Fyles Julie M. , Howell Simon L.
Published: July 2002

Adenosine 3',5‐cyclic monophosphate (cAMP) was shown to stimulate insulin secretion from electrically permeabilised islets of Langerhans incubated in Ca2+/EGTA buffers. cAMP‐induced insulin secretion occurred in the presence of either sub‐stimulatory (50 nM) or stimulatory (> 100 nM) concentrations of Ca2+. Similar effects on secretion were obtained in response to 8‐bromo‐cAMP (8‐Br‐cAMP) or the phosphodiesterase inhibitor, 3‐isobutyl‐1‐methylxanthine. Forskolin (0.2–20μM) increased adenylate cyclase activity and enhanced insulin secretion from the permeabilised islets. These results suggest that, in electrically permeabilised islets, cAMP‐induced insulin secretion is not dependent on changes in cytosolic Ca2+.
Acidification of the interior of Ehrlich ascites tumor cells by nigericin inhibits DNA synthesis
Authors: Margolis L.B. , Rozovskaja I.A. , Skulachev V.P.
Published: July 2002

In Ehrlich ascites carcinoma cells, acidification of the cytoplasm down to pH 6.2–6.3 arrests DNA synthesis. Such acidification can be obtained by decreasing the pH outside the cell or, alternatively, by addition of a micromolar concentration of the K+/H+ antiporter nigericin. Thus, nigericin may be regarded as a new type of cytostatic, the effect of which is mediated by alteration of the intracellular pH.
Calcium involvement in mediating the action of octopamine and hypertrehalosemic peptides on insect haemocytes
Authors: Jahagirdar A.P. , Milton G. , Viswanatha T. , Downer R.G.H.
Published: July 2002

Octopamine, the hypertrehalosemic peptides HT‐I and HT‐II and the calcium ionophore A23187 elevate intracellular calcium levels in cultured haemocytes of Malacosoma disstria (Lepidoptera: Lasiocampidae). The octopamine‐mediated response is dose‐dependent and the magnitude of the response is influenced by the concentration of calcium in the incubation medium. Mianserin, an inhibitor of octopamine‐mediated elevation of cyclic AMP production, blocks the octopamine‐mediated increase in intracellular calcium but has no effect on the HT‐I‐ and HT‐II‐mediated responses. The results indicate that some effects of octopamine are mediated through agonist‐dependent calcium gating whereas others are expressed through receptors coupled to adenylate cyclase. The study also confirms previous suggestions that HT‐I and HT‐II elevate intracellular calcium concentrations.
Endothermic oxygenation of hemocyanin in the krill Meganyctiphanes norvegica
Authors: Brix O. , Borgund S. , Barnung T. , Colosimo A. , Giardina B.
Published: July 2002

The oxygen affinity of the hemolymph of the krill Meganyctiphanes norvegica, increases with temperature in the pH range 7.4 to 8.1 reflecting an endothermic overall heat of reaction. This striking feature may be of adaptive significance with respect to the feeding excursions of the animal, which at night reaches the warmer phytoplankton‐rich surface layers, where the oxygen availability is reduced due to increased temperature and photorespiration.
Molecular cloning of an insect pheromone‐binding protein
Authors: Raming K. , Krieger J. , Breer H.
Published: July 2002

Pheromone binding protein; cDNA cloning; Nucleotide sequence; Primary structure; RNA blot hybridization
A biomimetic model for vanadium‐containing bromoperoxidase
Authors: Sakurai Hiromu , Tsuchiya Koichiro
Published: July 2002

A biomimetic model of vanadium‐containing bromoperoxidase (BPO) was proposed. The vanadium‐containing BPO possesses vanadate ion (+5 oxidation state) as a prosteric group and catalyses the formation of a carbon‐bromide bond in the presence of hydrogen peroxide, bromide ion and bromide acceptor. The reaction mechanism is as yet unknown. Several vanadyl (VO2+, +4 oxidation state) complexes with oxalate, glutarate, succinate, malonate and acetate ligands showed similar bromination activity to that of BPO. Especially, the vanadyl‐oxalato complex provided the highest BPO‐like activity. Both vanadate ion and vanadyl complexes with nitrogen‐containing ligands such as EDTA, glycine and serine showed essentially no BPO‐like activity. Thus, the vanadyl‐oxalato complex is proposed to be not only a possible chemical model of BPO, but a useful compound to elucidate the reaction mechanism of BPO.
Immunological characterization of the mitochondrial 2‐oxoglutarate carrier from liver and heart
Authors: Zara V. , De Benedittis R. , Ragan C.I. , Palmieri F.
Published: July 2002

Antibodies have been prepared against the 2‐oxoglutarate transport proteins purified from bovine heart and rat liver mitochondria. The anti‐heart antiserum cross‐reacts with the 2‐oxoglutarate carrier (OGC) from beef, pig, rat and rabbit heart, but not with the OGC from liver of the same animals. Conversely, the anti‐liver antiserum recognizes the carrier protein from liver of all species tested but not from heart. Immunoinactivation of oxoglutarate transport activity by the antibodies is also tissue specific. Peptide maps of purified OGC show structural differences between the carrier from heart and liver of the same animal species. These results indicate the existence of isoforms of the OGC in heart and liver.
Fatty acid acylated Fab‐fragments of antibodies to neurospecific proteins as carriers for neuroleptic targeted delivery in brain
Authors: Chekhonin Vladimir P. , Kabanov Alexander V. , Zhirkov Yurii A. , Morozov Georgii V.
Published: July 2002

A method for targeted delivery of neuroleptics from blood in brain based on using Fab‐fragments of antibodies to antigens of brain glia cells (acid gliofibrillar antigen and α2‐glycoprotein) is suggested. The essence of the technique is that the molecule of neuroleptic (trifluoperazine) is conjugated with Fab‐fragments of these antibodies. The conjugate thus obtained is modified by stearoylchloride in the system of Aerosol OT reversed micelles in octane. The study of the distribution of 125I‐labelled conjugates in the rat organism after intracordial introduction is performed. On the contrary to the nonmodified conjugates and conjugate, containing fatty acylated Fab‐fragments of antibodies, nonspecific to the rat brain, the conjugate of trifluoperazine with stearoylated Fab‐fragments of antibodies to neurospecific antigens accumulate in brain tissues. The drastic increase of the neuroleptic activity of trifluoperazine resulting from its coupling with stearoylated Fab‐fragments of antiglial antibodies is observed.
Differential expression of the mouse D2 dopamine receptor isoforms
Authors: Montmayeur J.P. , Bausero P. , Amlaiky N. , Maroteaux L. , Hen R. , Borrelli E.
Published: July 2002

We have identified and characterized the cDNAs corresponding to the mouse D2 dopamine receptors. We show that in the mouse the D2 dopamine receptor is found in two forms, generated by alternative splicing of the same gene, mRNA distribution analysis of areas expressing the D2 receptors shows that the larger form is the most abundant, except in the brain stem where the shorter form is predominant. Membranes of mammalian cells translently transfected with both forms of D2 receptor bind [1H]spiperone with a high affinity.
Lithium γ‐linolenate‐induced cytotoxicity against cells chronically infected with HIV‐1
Authors: Kinchington Derek , Randall Sharon , Winther Michael , Horrobin David
Published: July 2002

Lithium γ‐linolenate (Li‐GLA), was evaluated for its activity in selectively killing H9 cells chronically infected with HIV‐1RF. After 4 days incubation with Li‐GLA approximately 90% of the H9RF cells were non‐viable compared to 20% of uninfected H9 cells. The efficacy of the Li‐GLA, in preferentially killing HIV infected cells also correlates with lipid peroxidation, as measured by the intracellular thiobarbituric acid‐reactive material content. The addition of an antioxidant (vitamin E) to the culture medium reduced the toxicity of Li‐GLA. These data indicate that this selective killing effect of cells chronically infected with HIV may be due to the enhanced extent of lipid peroxidation of the added Li‐GLA.
Formation of a novel 20‐hydroxylated metabolite of lipoxin A4 by human neutrophil microsomes
Authors: Sumimoto Hideki , Isobe Ryuichi , Mizukami Yoichi , Minakami Shigeki
Published: July 2002

Lipoxin A4 (LXA4) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA4 either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse‐phase high‐performance liquid chromatography. We have identified the metabolite as 20‐hydroxy‐LXA4, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography‐mass spectrometry. The LXA4ω ‐hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH‐cytochrome P‐450 reductase, or competitively by leukotriene B4 (LTB4) and LTB5, substrates of LTB4 ω‐hydroxylase. These findings indicate that the formation of 20‐hydroxy‐LXA4 is catalyzed by a neutrophil cytochrome P‐450, the LTB4 ω‐hydroxylase.
Transforming growth factor β2 stimulates acute and chronic activation of the mitogen‐activated protein kinase cascade in rat renal mesangial cells
Authors: Huwiler Andrea , Pfeilschifter Josef
Published: July 2002

Exposure of rat glomerular mesangial cells to transforming growth factor β2 (TGFβ2) stimulates a biphasic mitogen‐activated protein kinase (MAP kinase) activation. A rapid increase in activity (maximal at 10 min) is followed by a second persistent level of activity which steadily increases over 24 h. The second peak of MAP kinase activity is markedly attenuated by the protein synthesis inhibitor cycloheximide and consequently is paralleled by a pronounced de‐novo synthesis of p42 and p44 MAP kinases as measured by immunoprecipitation of [35S]methionine‐labeled mesangial cells. In addition, an increased de‐novo synthesis of MAP kinase kinase (MEK), the upstream activator of MAP kinase, is observed in response to TGFβ2 stimulation. We propose that TGFβ‐induced activation and de‐novo synthesis of MAP kinases and MEK is important for the multifunctional actions of this cytokine in mesangial cells and its role in disease states characterized by excessive fibrosis.
Structural characterization of a monomeric chemokine: Monocyte chemoattractant protein‐3
Authors: Kim Key-Sun , Rajarathnam Krishnakumar , Clark-Lewis Ian , Sykes Brian D
Published: July 2002

1H‐NMR spectroscopy and analytical ultracentrifugation studies reveal that monocyte chemoattractant protein‐3 (MCP‐3) is a monomer. NMR solution structure shows that MCP‐3 adopts an α/β fold similar to what is observed in structures of other known chemokines. However, MCP‐3 is unique in that it does not show a propensity to form dimers. The closely related chemokines MCP‐1 and MCP‐2 show a monomer‐dimer equilibrium in sedimentation equilibrium studies (∼0.2–2 mg/ml). As these proteins are present at nanomolar concentrations in vivo, the results suggest that they are monomeric at functional concentrations and that the monomer is the functionally significant form of MCP‐1, MCP‐2 and MCP‐3.
GLIAL CELL INTERACTIONS WITH TENASCIN‐C: ADHESION AND REPULSION TO DIFFERENT TENASCIN‐C DOMAINS IS CELL TYPE RELATED
Authors: Scholze Angela , Götz Bernhard , Faissner Andreas
Published: July 2002

The multimodular glycoprotein tenascin‐C is transiently expressed, predominantly by glial cells, during the development of the central and peripheral nervous systems. This extracellular matrix glycoprotein is involved in the control of cell adhesion, neuron migration and neurite outgrowth. Distinct functional properties for neuronal cell types have been attributed to separate tenascin‐C domains using antibody perturbation studies and in vitro experiments on tenascin‐C fragments. In order to study potential roles of tenascin‐C for glial cell biology, a library of recombinant tenascin‐C domains was used in a bioassay in vitro. Embryonic day 14 astrocytes, various astroglial‐derived cell lines (C6, A7 and Neu7) and oligodendroglial‐derived cell types (Oli‐neu and G26‐20) were examined in an adhesion assay and compared to the neuroblastoma cell line N2A. A binding site for most cell types, except for A7 and N2A, could be assigned to the first three fibronectin type III domains. Repulsive properties could be mapped to three different sites, the epidermal growth factor‐like repeats, fibronectin type III repeats 4 and 5 and to the alternatively spliced region of the molecule. The responses to these repulsive sites varied according to the cell type. These data are consistent with the interpretation that different cell types express distinct sets of tenascin‐C receptors which might regulate cellular responses via distinct second messenger pathways.
Suicidality in patients with panic disorder: the association with comorbidity
Authors: Ağargün MY , Kara H
Published: July 2002

To examine the relationship between suicidality and panic disorder, we evaluated 91 patients with panic disorder. Patients with comorbid diagnosis were more suicidal than patients with pure panic disorder. These data suggest that among patients with panic disorder, suicidal behavior is associated with comorbid diagnosis.
Acylation of Gα13 is important for its interaction with thrombin receptor, transforming activity and actin stress fiber formation
Authors: Ponimaskin Evgeni , Behn Holger , Adarichev Vyacheslav , Voyno-Yasenetskaya Tatyana A. , Offermanns Stefan , Schmidt Michael F.G.
Published: July 2002

Palmitoylation of α‐subunits in heterotrimeric G proteins has become a research object of growing attention. Following our recent report on the acylation of the mono‐palmitoylated Gα12 [Ponimaskin et al., FEBS Lett. 429 (1998) 370–374], we report here on the identification of three palmitoylation sites in the second member of the G12 family, Gα13, and on the biological significance of fatty acids on the particular sites. Using mutants of α13 in which the potentially palmitoylated cysteine residues (Cys) were replaced by serine residues, we find that Cys‐14, Cys‐18 and Cys‐37 all serve as palmitoylation sites, and that the mutants lacking fatty acids are functionally defective. The following biological functions of Gα13 were found to be inhibited: coupling to the PAR1 thrombin receptor, cell transformation and actin stress fiber formation. Results from established assays for the above functions with a series of mutants, including derivatives of the constitutively active mutant Gα13Q226L, revealed a graded inhibitory response on the above mentioned parameters. As a rule, it appears that palmitoylation of the N‐proximal sites (e.g. Cys‐14 and Cys‐18) contributes more effectively to biological function than of the acylation site located more internally (Cys‐37). However, the mutant with Cys‐37 replaced by serine is more severely inhibited in stress fiber formation (80%) than in cell transformation (50%), pointing to the possibility of a differential involvement of the three palmitoylation sites in Gα13.
Sphingosylphosphorylcholine induces Ca2+‐sensitization of vascular smooth muscle contraction: possible involvement of Rho‐kinase
Authors: Todoroki-Ikeda Natsuko , Mizukami Yoichi , Mogami Kimiko , Kusuda Takeshi , Yamamoto Kuniko , Miyake Teruki , Sato Masafumi , Suzuki Shinichi , Yamagata Hirotaka , Hokazono Yuki , Kobayashi Sei
Published: July 2002

Sphingosylphosphorylcholine (SPC), a sphingolipid, concentration‐dependently (1–50 μM) induced contraction and slight elevation of the cytosolic Ca2+ concentration ([Ca2+]i) in smooth muscle of the pig coronary artery, the result being a marked increase in the force/[Ca2+]i ratio. In α‐toxin‐ or β‐escin‐permeabilized, but not Triton X‐100‐permeabilized, vascular strips, SPC induced contraction at constant [Ca2+]i (pCa 6.3) in the absence of GTP, whereas a G‐protein‐coupled receptor agonist, histamine, required the presence of GTP to induce the contraction. The Rho‐kinase blocker, Y‐27632 (10 μM) abolished the SPC‐induced Ca2+‐sensitization, without affecting the Ca2+‐induced contraction. These results suggest that SPC induces Ca2+‐sensitization of force in vascular smooth muscle, presumably through the activation of Rho‐kinase (or a related kinase).
PKC phosphorylation of a conserved serine residue in the C‐terminus of group III metabotropic glutamate receptors inhibits calmodulin binding
Authors: Airas José M , Betz Heinrich , El Far Oussama
Published: July 2002

Group III metabotropic glutamate receptors (mGluRs) serve as presynaptic receptors that mediate feedback inhibition of glutamate release via a Ca2+/calmodulin (CaM)‐dependent mechanism. In vitro phosphorylation of mGluR7A by protein kinase C (PKC) prevents its interaction with Ca2+/CaM. In addition, activation of PKC leads to an inhibition of mGluR signaling. Here, we demonstrate that disrupting CaM binding to mGluR7A by PKC in vitro is due to phosphorylation of a highly conserved serine residue, S862. We propose charge neutralization of the CaM binding consensus sequence resulting from phosphorylation to constitute a general mechanism for the regulation of presynaptic mGluR signaling.
Catalytic activity of ADAM28
Authors: Howard Linda , Zheng Yufang , Horrocks Maureen , Maciewicz Rose A. , Blobel Carl
Published: July 2002

ADAMs are membrane‐anchored glycoproteins containing a disintegrin and metalloprotease domain that have important roles in fertilization, development, and diseases such as Alzheimer's dementia. Here we present the first evidence for catalytic activity of ADAM28, a protein that is highly expressed in the epididymis and lymphocytes. Recombinant ADAM28 cleaves myelin basic protein at two sites. The catalytic activity of ADAM28 is not sensitive to tissue inhibitors of metalloproteases 1 and 2, but can be abolished by a mutation in the catalytic site. Catalytically active ADAM28 will be valuable for further studies of its role in sperm maturation and lymphocyte function.
Superinduction of COX‐2 mRNA by cycloheximide and interleukin‐1β involves increased transcription and correlates with increased NF‐κB and JNK activation
Authors: Newton Robert , Stevens David A. , Hart Lorraine A. , Lindsay Mark , Adcock Ian M. , Barnes Peter J.
Published: July 2002

Many primary response genes, including cyclooxygenase‐2 (COX‐2), exhibit mRNA superinduction following agonist stimulation in the presence of translational blockers such as cycloheximide. This is widely assumed to result from mRNA stabilisation. However, superinduction of IL‐1β‐induced COX‐2 mRNA levels by cycloheximide in pulmonary type II A549 cells occurred by increased transcription and not by mRNA stabilisation. Furthermore, equivalent effects were observed on NF‐κB binding to COX‐2 promoter κB sites and activation of the Jun N‐terminal kinases (JNK), p54 and p46. These signalling pathways play important roles in COX‐2 induction and may therefore account for the observed increases in COX‐2 transcription. These data are consistent with negative feed‐back involving down‐regulation of NF‐κB by de novo IκBα synthesis and suggest that JNK activation may also be down‐regulated by a cycloheximide sensitive process.
Plant CDC2 is not only targeted to the pre‐prophase band, but also co‐localizes with the spindle, phragmoplast, and chromosomes
Authors: Stals Hilde , Bauwens Serge , Traas Jan , Van Montagu Marc , Engler Gilbert , Inzé Dirk
Published: July 2002

A polyclonal antiserum against the p34cdc2 homologue of Arabidopsis thaliana, CDC2aAt, was used in parallel with a polyclonal antiserum against the PSTAIRE motif to study the subcellular localization of CDC2 during the cell cycle of isolated root tip cells of Medicago sativa. During interphase, CDC2 was located in the nucleus and in the cytoplasm. The cytoplasmic localization persisted during the complete cell cycle, whereas the nuclear signal disappeared at nuclear envelope breakdown. At the beginning of anaphase, the anti‐CDC2aAt antibody transiently co‐localized with condensed chromosomes. The chromosomal co‐localization disappeared as anaphase continued and remained excluded from the separated chromosomes until cytokinesis, when CDC2 re‐located to the newly forming nuclei. We also observed a co‐localization of CDC2 with three microtubular structures, the pre‐prophase band, the spindle, and the phragmoplast.
Cardiac myocytes express mRNA for ten RGS proteins: changes in RGS mRNA expression in ventricular myocytes and cultured atria
Authors: Kardestuncer Tarik , Wu Haiguo , Lim Angela L , Neer Eva J
Published: July 2002

Regulators of G‐protein signalling (RGS) are recently identified proteins that shorten the lifetime of the activated G protein. We now show that rat cardiac myocytes express mRNA for at least 10 RGS. The mRNA for RGS‐r is barely detectable in rat ventricles, but increases more than 20‐fold during the 60‐ to 90‐min process of isolating ventricular myocytes, and after 90 min of culture of atrial pieces in medium with Ca2+. Both in myocytes and in atria, the rise in RGS‐r is transient. The mRNA for cardiac RGS5, but not RGS‐r, is developmentally regulated. These studies suggest that rapid regulation of RGS levels may be a new mechanism that governs how signals are transmitted across the cardiac cell membrane.
1H NMR spectroscopy of the binuclear Cu(II) active site of Streptomyces antibioticus tyrosinase
Authors: Bubacco Luigi , Salgado Jesús , Tepper Armand W.J.W. , Vijgenboom Erik , Canters Gerard W.
Published: July 2002

The 600 MHz 1H NMR spectrum of tyrosinase (31 kDa) of Streptomyces antibioticus in the oxidized, chloride‐bound form is reported. The downfield part of the spectrum (15–55 ppm) exhibits a large number of paramagnetically shifted signals. The paramagnetism is ascribed to a thermally populated triplet state. The signals derive from six histidines binding to the metals through their Nϵ atoms. There is no evidence for endogenous bridges. The exchange coupling, −2J, amounts to 298 cm−1. In the absence of chloride the peaks broaden. This is ascribed to a slowing down of the electronic relaxation. The exchange coupling decreases to −2J=103 cm−1.
Calumenin interacts with serum amyloid P component
Authors: Vorum Henrik , Jacobsen Christian , Honoré Bent
Published: July 2002

We recently reported the identification of human calumenin, a novel Ca2+ binding, transformation‐sensitive and secreted protein [Vorum et al. (1998) Biochim. Biophys. Acta 1386, 121–131; Vorum et al. (1999) Exp. Cell Res. 248, 473–481] belonging to the family of multiple EF‐hand proteins of the secretory pathway that include reticulocalbin, ERC‐55, Cab45 and crocalbin. In order to further investigate the extracellular functions of calumenin we immobilized the recombinant protein to a column. After application of a placental tissue extract we were able to elute one protein that interacts with calumenin in the presence of Ca2+. Amino acid sequencing identified this protein as serum amyloid P component (SAP). Furthermore, we verified and characterized the calumenin‐SAP interaction by the surface plasmon resonance technique. The findings indicate that calumenin may participate in the immunological defense system and could be involved in the pathological process of amyloidosis that leads to formation of amyloid deposits seen in different types of tissues.
Existence results for mean field equations
Authors: Li Jiayu , Wang Guofang , Ding Weiyue , Jost Jürgen
Published: July 2002

Let

Ω

be an annulus. We prove that the mean field equation

\begin{cases}
- \Delta \psi = \frac{e^{ - \beta \psi }}{\int _{\Omega }e^{ - \beta \psi }} & \text{in }\Omega \\
\psi = 0 & \text{on }\partial \Omega
\end{cases}

admits a solution for

β \in (−16π, −8π)

. This is a supercritical case for the Moser–Trudinger inequality.

On montre que l’équation de champ moyen

\begin{cases}
- \Delta \psi = \frac{e^{ - \beta \psi }}{\int _{\Omega }e^{ - \beta \psi }} & \text{dans }\Omega \\
\psi = 0 & \text{sur }\partial \Omega
\end{cases}

pour

Ω

étant un anneau, admet une solution pour

β ∈ (−16π, −8π)

. Celà represente un cas supercritique pour l’inegalité de Moser–Trudinger.
Promotion of neurite outgrowth by protein kinase inhibitors and ganglioside GM1 in neuroblastoma cells involves MAP kinase ERK1/2
Authors: Singleton David W. , Lu C.L. , Colella Rita , Roisen Fred J.
Published: July 2002

To investigate mechanisms of neurite outgrowth, murine Neuro‐2a neuroblastoma cells were exposed to ganglioside GM1 in the presence or absence of specific protein kinase inhibitors. Isoquinolinesulfonamide (H‐89), an inhibitor of cyclic AMP dependent protein kinase A (PKA), and bisindolylmaleimide I (BIM), which inhibits protein kinase C, each stimulated neurite outgrowth in a dose‐dependent manner in the absence of exogenous GM1. Minimally effective (threshold) concentrations of H‐89 or BIM potentiated outgrowth when they were used in combination with GM1. To search for a shared component in the mechanisms of GM1, H‐89 and BIM, phosphorylation of ERK1/2 was examined. Inhibition of the activation of extracellular signal regulated kinases (ERK1/2) by U0126, prevented neuritogenesis of Neuro‐2a by all the three agents. Pretreatment of serum‐depleted Neuro‐2a cultures with GM1 or BIM enhanced ERK1/2 phosphorylation when the serum level was restored to 10%. In contrast, H‐89 did not alter the serum‐mediated response. In cells exposed to GM1 or BIM without additional serum, a transitory decrease in ERK phosphorylation occurred. These data suggest that GM1 influences two neuritogenic pathways, one modulated by PKC and the other regulated by PKA. Therefore, GM1 may have the potential to stimulate alternate pathways resulting in outgrowth.
Role of vimentin in early stages of neuritogenesis in cultured hippocampal neurons
Authors: Boyne Lesley J. , Fischer Itzhak , Shea Thomas B.
Published: July 2002

Vimentin is expressed initially by nearly all neuronal precursors in vivo, and is replaced by neurofilaments shortly after the immature neurons become post‐mitotic. Moreover, both vimentin and neurofilaments can be detected transiently within the same neurite, leaving open the possibility that vimentin may play a role in the early stages of neuritogenesis. In the present study, cultured hippocampal neurons, which transiently express vimentin in culture, were treated with sense‐ and antisense‐oriented deoxyoligonucleotides encoding regions of the vimentin sequence that overlap the translation initiation codon. Antisense oligonucleotide treatment reduced vimentin‐immunoreactivity to background levels. Moreover, while 90–100% of cultured hippocampal neurons elaborated neurites within the first 24 hr following plating, only 24–30% did so in the presence of vimentin antisense oligonucleotides. Inhibition of neurite outgrowth was reversible following removal of antisense oligonucleotide. These findings substantiate earlier studies in neuroblastoma cells, indicating a possible role for vimentin in the initiation of neurite outgrowth.
Calbindin and parvalbumin are early markers of non‐mitotically regenerating hair cells in the bullfrog vestibular otolith organs
Authors: Steyger P.S. , Burton M. , Hawkins J.R. , Schuff N.R. , Baird R.A.
Published: July 2002

Earlier studies have demonstrated hair cell regeneration in the absence of cell proliferation, and suggested that supporting cells could phenotypically convert into hair cells following hair cell loss. Because calcium‐binding proteins are involved in gene up‐regulation, cell growth, and cell differentiation, we wished to determine if these proteins were up‐regulated in scar formations and regenerating hair cells following gentamicin treatment. Calbindin and parvalbumin immunolabeling was examined in control or gentamicin‐treated (GT) bullfrog saccular and utricular explants cultured for 3 days in amphibian culture medium or amphibian culture medium supplemented with aphidicolin, a blocker of nuclear DNA replication in eukaryotic cells. In control cultures, calbindin and parvalbumin immunolabeled the hair bundles and, less intensely, the cell bodies of mature hair cells. In GT or mitotically‐blocked GT (MBGT) cultures, calbindin and parvalbumin immunolabeling was also seen in the hair bundles, cuticular plates, and cell bodies of hair cells with immature hair bundles. Thus, these antigens were useful markers for both normal and regenerating hair cells. Supporting cell immunolabeling was not seen in control cultures nor in the majority of supporting cells in GT cultures. In MBGT cultures, calbindin and parvalbumin immunolabeling was up‐regulated in the cytosol of single supporting cells participating in scar formations and in supporting cells with hair cell‐like characteristics. These data provide further evidence that non‐mitotic hair cell regeneration in cultures can be accomplished by the conversion of supporting cells into hair cells.
Monitoring The Fetus In Labor: Evidence to Support the Methods
Authors: Albers Leah L.
Published: July 2002

Electronic fetal monitoring (EFM) was implemented across the United States in the 1970s. By 1998, it was used in 84% of all U.S. births, regardless of whether the primary caregiver was a physician or a midwife. Numerous randomized trials have agreed that continuous EFM in labor increases the operative delivery rate, without clear benefit to the baby. Intermittent auscultation (IA) is safe and effective in low‐risk pregnancies and may play a role in helping birth remain normal. Clinicians and educators are encouraged to reconsider the use of IA in the care of healthy childbearing women.
Multimodal evaluation of an Italian family with a hereditary spastic paraplegia and POLR3A mutations
Authors: Ruggiero Lucia , Iovino Aniello , Dubbioso Raffaele , Cocozza Sirio , Trovato Rosanna , Aruta Francesco , Pontillo Giuseppe , Barghigiani Melissa , Brunetti Arturo , Santorelli Filippo Maria , Manganelli Fiore , Iodice Rosa
Published: October 2020

We describe an Italian family with adult‐onset pure hereditary spastic paraplegia due to biallelic variants in POLR3A gene [c.1909 + 22G > A and c.3839dupT (p.M1280fs*20]. MRI showed a mild hyperintensity of superior cerebellar peduncles and cervical spinal cord atrophy. The neurophysiological metrics about intracortical excitability showed higher values of motor thresholds and a significant reduction of short interval intracortical inhibition (SICI) in the patient with a more severe phenotype. Our multimodal evaluation further expands the wide phenotypic spectrum associated with mutations in the POLR3A gene. An extensive genotype–phenotype correlation study is necessary to explain the role of the many new mutations on the function of protein.