bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of Xenopus Chk1 by mutagenesis of threonine‐377
Authors: Wang Sophie X , Dunphy William G
Published: July 2002

Xenopus Chk1 (Xchk1) is required for the checkpoint‐associated delay of the cell cycle in frog egg extracts containing unreplicated or UV‐damaged DNA. Phosphorylation of Xchk1 at multiple sites in the SQ/TQ domain (residues 314–366) in response to unreplicated or UV‐damaged DNA results in elevation of its kinase activity. We have found that mutagenesis of Thr‐377 in the conserved Thr–Arg–Phe (TRF) motif of Xchk1 also leads to a substantial increase in kinase activity. Thr‐377 does not appear to be a site of phosphorylation in Xchk1. These findings suggest that Thr‐377 may play a role in suppressing the activity of Xchk1.
Identification of binding proteins for cholesterol absorption inhibitors as components of the intestinal cholesterol transporter
Authors: Kramer Werner , Glombik Heiner , Petry Stephan , Heuer Hubert , Schäfer Hans-Ludwig , Wendler Wolfgang , Corsiero Daniel , Girbig Frank , Weyland Claudia
Published: July 2002

To identify protein components of the intestinal cholesterol transporter, rabbit small intestinal brush border membrane vesicles were submitted to photoaffinity labeling using photoreactive derivatives of 2‐azetidinone cholesterol absorption inhibitors. An integral membrane protein of M
r 145.3±7.5 kDa was specifically labeled in brush border membrane vesicles from rabbit jejunum and ileum. Its labeling was concentration‐dependently inhibited by the presence of cholesterol absorption inhibitors whereas bile acids, D‐glucose, fatty acids or cephalexin had no effect. The inhibitory potency of 2‐azetidinones to inhibit photolabeling of the 145 kDa protein correlated with their in vivo activity to inhibit intestinal cholesterol absorption. These results suggest that an integral membrane protein of M
r 145 kDa is (a component of) the cholesterol absorption system in the brush border membrane of small intestinal enterocytes.
Secondary structure of human apolipoprotein A‐I(1–186) in lipid‐mimetic solution
Authors: Okon Mark , Frank Philippe G. , Marcel Yves L. , Cushley Robert J.
Published: July 2002

The solution structure of an apoA‐I deletion mutant, apoA‐I(1–186) was determined by the chemical shift index (CSI) method and the torsion angle likelihood obtained from shift and sequence similarity (TALOS) method, using heteronuclear multidimensional NMR spectra of [u‐13C, u‐15N, u‐50% 2H]apoA‐I(1–186) in the presence of sodium dodecyl sulfate (SDS). The backbone resonances were assigned from a combination of triple‐resonance data (HNCO, HNCA, HN(CO)CA, HN(CA)CO and HN(COCA)HA), and intraresidue and sequential NOEs (three‐dimensional (3D) and four‐dimensional (4D) 13C‐ and 15N‐edited NOESY). Analysis of the NOEs, Hα, Cα and C′ chemical shifts shows that apoA‐I(1–186) in lipid‐mimetic solution is composed of α‐helices (which include the residues 8–32, 45–64, 67–77, 83–87, 90–97, 100–140, 146–162, and 166–181), interrupted by short irregular segments. There is one relatively long, irregular and mostly flexible region (residues 33–44), that separates the N‐terminal domain (residues 1–32) from the main body of protein. In addition, we report, for the first time, the structure of the N‐terminal domain of apoA‐I in a lipid‐mimetic environment. Its structure (α‐helix 8–32 and flexible linker 33–44) would suggest that this domain is structurally, and possibly functionally, separated from the other part of the molecule.
A yeast two‐hybrid study of human p97/Gab2 interactions with its SH2 domain‐containing binding partners
Authors: Crouin Catherine , Arnaud Mary , Gesbert Franck , Camonis Jacques , Bertoglio Jacques
Published: July 2002

p97/Gab2 is a recently characterized member of a large family of scaffold proteins that play essential roles in signal transduction. Gab2 becomes tyrosine‐phosphorylated in response to a variety of growth factors and forms multimolecular complexes with SH2 domain‐containing signaling molecules such as the p85‐regulatory subunit of the phosphoinositide‐3‐kinase (p85‐PI3K), the tyrosine phosphatase SHP‐2 and the adapter protein CrkL. To characterize the interactions between Gab2 and its SH2‐containing binding partners, we designed a modified yeast two‐hybrid system in which the Lyn tyrosine kinase is expressed in a regulated manner in yeast. Using this assay, we demonstrated that p97/Gab2 specifically interacts with the SH2 domains of PI3K, SHP‐2 and CrkL. Interaction with p85‐PI3K is mediated by tyrosine residues Y452, Y476 and Y584 of Gab2, while interaction with SHP‐2 depends exclusively on tyrosine Y614. CrkL interaction is mediated by its SH2 domain recognizing Y266 and Y293, despite the latter being in a non‐consensus (YTFK) environment.
Modulation of ribosomal recruitment to 5′‐terminal start codons by translation initiation factors IF2 and IF3
Authors: Grill Sonja , Moll Isabella , Hasenöhrl David , Gualerzi Claudio O. , Bläsi Udo
Published: July 2002

Sequence determinants and structural features of the RNA govern mRNA–ribosome interaction in bacteria. However, ribosomal recruitment to leaderless mRNAs, which start directly with the AUG start codon and do not bear a Shine–Dalgarno sequence like canonical mRNAs, does not appear to rely on 16S rRNA–mRNA interactions. Here, we have studied the effects of translation initiation factors IF2 and IF3 on 30S initiation at a 5′‐terminal AUG and at a competing downstream canonical ribosome binding site. We show that IF2 affects the forward kinetics of 30S initiation complex formation at the 5′‐terminal AUG as well as the stability of these complexes. Moreover, the IF2:IF3 molar ratio was found to play a decisive role in translation initiation of a leaderless mRNA both in vitro and in vivo indicating that the translational efficiency of an mRNA is not only intrinsically determined but can be altered depending on the availability of components of the translational machinery.
Mutualists and parasites: how to paint yourself into a (metabolic) corner
Authors: Tamas Ivica , Klasson Lisa M , Sandström Jonas P , Andersson Siv G.E
Published: July 2002

Eukaryotes have developed an elaborate series of interactions with bacteria that enter their bodies and/or cells. Genome evolution of symbiotic and parasitic bacteria multiplying inside eukaryotic cells results in both convergent and divergent changes. The genome sequences of the symbiotic bacteria of aphids, Buchnera aphidicola, and the parasitic bacteria of body louse and humans, Rickettsia prowazekii, provide insights into these processes. Convergent genome characteristics include reduction in genome sizes and lowered G+C content values. Divergent evolution was recorded for amino acid and cell wall biosynthetic genes. The presence of pseudogenes in both genomes provides examples of recent gene inactivation events and offers clues to the process of genome deterioration and host‐cell adaptation.
Expression of recombinant human ceruloplasmin – an absolute requirement for splicing signals in the expression cassette
Authors: Rafiq Mineza , Suen Christine K.M , Choudhury Natasha , Joannou Christopher L , White Kenneth N , Evans Robert W
Published: July 2002

We report the successful expression of recombinant human ceruloplasmin which was made possible by inclusion of splicing signals in the expression vector. Ceruloplasmin cDNA expressed from the vector pNUT in baby hamster kidney cells gave protein yields of 0.03 mg/l which increased to 15 mg/l with splicing signals present. The defect in expression from the intronless cDNA is due to complete retention of ceruloplasmin mRNA in cell nuclei. The block to cytoplasmic export is alleviated by splicing signals, allowing full expression of the mRNA.
Assembly of Staphylococcus aureusγ‐hemolysin into a pore‐forming ring‐shaped complex on the surface of human erythrocytes
Authors: Sugawara Noriko , Tomita Toshio , Kamio Yoshiyuki
Published: July 2002

Staphylococcal γ‐hemolysin consists of Hlg1 (or Luk F) of 34 kDa and Hlg2 of 32 kDa, which cooperatively lyse human erythrocytes. Since γ‐hemolysin caused swelling of human erythrocytes prior to lysis, we studied pore‐forming nature of the toxin by use of polyethylene glycols as osmotic protectants and determined the functional diameter of the pore. To elucidate the molecular architecture of the membrane pore formed by γ‐hemolysin, we solubilized the pore complex with 2% sodium dodecyl sulfate, separated it from erythrocyte membrane proteins by sucrose gradient ultracentrifugation, and observed the isolated complex under an electron microscope. Our data showed that Hlg1 and Hlg2 of γ‐hemolysin assemble into a ring‐shaped 195 kDa complex in a molar ratio of 1 : 1, which may form a membrane pore with a functional diameter of 2.1–2.4 nm.
Modulation of rat brain calpastatin efficiency by post‐translational modifications
Authors: Salamino Franca , Averna Monica , Tedesco Ilaria , De Tullio Roberta , Melloni Edon , Pontremoli Sandro
Published: July 2002

Calpains, the thiol proteinases of the calcium‐dependent proteolytic system, are regulated by a natural inhibitor, calpastatin, which is present in brain tissue in two forms. Although both calpastatins are highly active on human erythrocyte calpain, only one form shows a high inhibitory efficiency with both rat brain calpain isozymes. The second calpastatin form is almost completely inactive against homologous proteinases and can be converted into an active one by exposure to a phosphoprotein phosphatase, also isolated from rat brain. Phosphorylation of the active calpastatin by protein kinase C and protein kinase A promotes a decrease in its inhibitory efficiency. The interconversion between the two inhibitor forms seems involved in the adjustment of the level of intracellular calpastatin activity on specific cell requirements.
Pervanadate elicits proliferation and mediates activation of mitogen‐activated protein (MAP) kinase in the nucleus1
Authors: Krady Marie-Marthe , Freyermuth Solange , Rogue Patrick , Malviya Anant N
Published: July 2002

There is growing evidence for the role of protein tyrosine phosphatases in controlling such fundamental cellular processes as growth and differentiation. Pervanadate is a potent inhibitor of protein tyrosine phosphatase which has been observed here to induce proliferation in C3H10T1/2 mouse fibroblasts. Pervanadate also translocated/activated p42/44 mitogen‐activated protein (MAP) kinase to the cell nucleus. An almost similar pattern of nuclear p42/44 MAP kinase stimulation is seen with TPA. On the other hand, TPA treatment results in a rapid activation of cytosolic MAP kinase which declines with time. Thus pervanadate appears as a very useful tool for studying tyrosine phosphorylation.
Insulin‐like growth factor I reverses interleukin‐1β inhibition of insulin secretion, induction of nitric oxide synthase and cytokine‐mediated apoptosis in rat islets of Langerhans
Authors: Mabley Jon G. , Belin Véronique , John Nerys , Green Irene C.
Published: July 2002

We have previously observed that treatment of rat islets of Langerhans with interleukin‐1β for 12 h results in nitric oxide‐dependent inhibition of insulin secretion, while 48 h treatment increased rates of islet cell death by apoptosis. Here, we demonstrate that interleukin‐1β‐mediated nitric oxide formation and inhibition of insulin secretion are significantly reduced by 24 h pretreatment of rat islets of Langerhans with insulin‐like growth factor I (IGF‐I). IGF‐I decreased cytokine induction of nitric oxide synthase in islets. Use of an arginine analogue in culture or IGF‐I pretreatment of islets were also effective in protecting islets against cytokine‐mediated apoptotic cell death. We conclude that IGF‐I antagonises inhibitory and cytotoxic effects of cytokines in rat islets.
Rat brain contains multiple mRNAs for calpastatin1
Authors: De Tullio Roberta , Sparatore Bianca , Salamino Franca , Melloni Edon , Pontremoli Sandro
Published: July 2002

This work was undertaken to establish the forms of the calpain inhibitor, calpastatin, expressed in the brain tissue. Five cDNA clones were obtained and the corresponding amino acid sequences were deduced. Three of these proteins contain an N‐terminal domain (domain L) and four inhibitory repeats typical of the calpastatin molecule. The other two are truncated forms, containing the domain L, free or associated with a single inhibitory repeat. Other differences, due to exon skipping, produce calpastatin forms with different susceptibility to posttranslational modifications. The more represented mRNA form corresponds to a calpastatin molecule containing the four inhibitory domains. These results may be useful to understand the involvement of calpain in the onset of acute and degenerative disorders of the central nervous system.
Repeated, protein‐encoding heterochromatic genes cause inactivation of a juxtaposed euchromatic gene
Authors: Tulin A.V , Naumova N.M , Aravin A.A , Gvozdev V.A
Published: July 2002

Euchromatic genes are often silenced by rearrangements that place them within or near heterochromatin, a phenomenon known as position effect variegation (PEV). However, little is known about molecular structure of cis‐acting heterochromatic fragments responsible for PEV. Here we report that heterochromatic cluster containing Stellate repeats, that encode putative regulatory subunit of protein kinase CK2 cause PEV of a reporter white `mini‐gene'. It is the first example of an euchromatic gene being silenced because of the proximity to the natural, well‐defined heterochromatic repeat cluster.
Diphospho‐myo‐inositol phosphates in Dictyostelium and Polysphondylium: identification of a new bisdiphospho‐myo‐inositol tetrakisphosphate
Authors: Laussmann Tim , Hansen André , Reddy Komandla Malla , Reddy K.Kishta , Falck J.R , Vogel Günter
Published: July 2002

The two major diphospho inositol phosphates from the axenic strain Dictyostelium discoideum AX2 were previously investigated and identified as 6‐PP‐InsP5 and 5,6‐bis‐PP‐InsP4. In order to examine whether these findings are representative of Dictyostelids in general, five non‐axenic wild‐type species of Dictyostelium and two of Polysphondylium were studied. It was found that all of the Dictyostelium species exhibit similar patterns of diphospho inositol phosphates. By contrast, both of the Polysphondylium species contain 5‐PP‐InsP5 as the predominant isomer. Besides 5,6‐bis‐PP‐InsP4, a new bis‐PP‐InsP4 was detected in Polysphondylium. This compound is either 1,5‐bis‐PP‐InsP4 or its corresponding enantiomer 3,5‐bis‐PP‐InsP5. The structures were elucidated by two‐dimensional 1H‐1H and 1H‐31P NMR analysis. Additionally, they were confirmed using a specific 6‐PP‐InsP5‐5‐kinase from D. discoideum AX2 as an enantio‐specific tool and enantiomerically pure reference standards.
Immobilization strategies for biological scanning probe microscopy1
Authors: Wagner Peter
Published: July 2002

Biological atomic force microscopy (AFM) is now established as a method for studying the structure and function of biomolecular objects at the solid‐liquid interface. Major progress in this field is linked to new developments in instrumentation, a better understanding of tip‐sample interactions, and improved sample preparation techniques. In this review, the most common strategies for biomolecular immobilization with respect to biological AFM applications are summarized.
Properties of calpastatin forms in rat brain
Authors: Melloni Edon , De Tullio Roberta , Averna Monica , Tedesco Ilaria , Salamino Franca , Sparatore Bianca , Pontremoli Sandro
Published: July 2002

Four recombinant calpastatin forms, deduced from rat brain mRNAs and differing in the number of inhibitory repetitive domains from zero to four, were expressed and characterized for their inhibitory efficiency on μ‐ and m‐calpain. Although the most effective one is a truncated calpastatin form composed of the N‐terminal region (domain L) and a single inhibitory domain, all inhibitors are more active against μ‐calpain, but are preferentially degraded and inactivated by m‐calpain. The protein form composed exclusively of a domain L is deprived of any inhibitory activity but prevents inhibition of calpain by the other calpastatin forms, indicating that this calpastatin region could be relevant in the recognition of the proteinase. A calpastatin form having molecular properties similar to those of the recombinant truncated calpastatin, has also been found in rat brain. It does not derive from proteolysis of a higher molecular mass precursor. The expression of multiple calpastatin forms may be relevant for the specific modulation of the different calpain isozymes normally present in a single cell type.
An intact conformation at the tip of elongation factor G domain IV is functionally important
Authors: Martemyanov K.A. , Yarunin A.S. , Liljas A. , Gudkov A.T.
Published: July 2002

Three variants of Thermus thermophilus EF‐G with mutations in the loop at the distal end of its domain IV were obtained. The replacement of His‐573 by Ala and double mutation H573A/D576A did not influence the functional activity of EF‐G. On the other hand, the insertion of six amino acids into the loop between residues Asp‐576 and Ser‐577 reduced the translocational activity of EF‐G markedly, while its GTPase activity was not affected. It is concluded that the native conformation of the loop is important for the factor‐promoted translocation in the ribosome. The functional importance of the entire EF‐G domain IV is discussed.
Molecular anatomy of the human glucose 6‐phosphate dehydrogenase core promoter
Authors: Franzè Annamaria , Ferrante Maria Immacolata , Fusco Francesca , Santoro Antonietta , Sanzari Emma , Martini Giuseppe , Ursini Matilde Valeria
Published: July 2002

The gene encoding glucose 6‐phosphate dehydrogenase (G6PD), which plays a pivotal role in cell defense against oxidative stress, is ubiquitously expressed at widely different levels in various tissues; moreover, G6PD expression is regulated by a number of stimuli. In this study we have analyzed the molecular anatomy of the G6PD core promoter. Our results indicate that the G6PD promoter is more complex than previously assumed; G6PD expression is under the control of several elements that are all required for correct promoter functioning and, furthermore, a still unidentified mammalian specific factor is needed.
Identification of specific nuclear protein kinase C isozymes and accelerated protein kinase C‐dependent nuclear protein phosphorylation during myocardial ischemia
Authors: Albert Carolyn J. , Ford David A.
Published: July 2002

Protein kinase C (PKC) has been suggested to mediate, at least in part, multiple processes in the pathophysiological sequelae of myocardial ischemia. The present study demonstrates that the ϵ, η and ι isozymes of PKC are translocated to nuclei in response to brief intervals of global ischemia as well as reperfusion of ischemic rat myocardium. Concomitant with the translocation of PKC isozymes to nuclei during ischemia, increased PKC‐mediated nuclear protein phosphorylation was observed. Taken together, the present results demonstrate that nuclear signaling mechanisms are activated during myocardial ischemia that include PKC translocation and PKC‐mediated nuclear protein phosphorylation.
Metabolic profiling of oxylipins upon salicylate treatment in barley leaves — preferential induction of the reductase pathway by salicylate1
Authors: Weichert Heiko , Stenzel Irene , Berndt Ekkehardt , Wasternack Claus , Feussner Ivo
Published: July 2002

In barley leaves, 13‐lipoxygenases (13‐LOXs) are induced by salicylate (SA) and jasmonate. Here, we show by metabolic profiling that upon SA treatment, free linolenic acid and linoleic acid accumulate in a 10:1 ratio reflecting their relative occurrence in leaf tissues. Furthermore, 13‐LOX‐derived products are formed and specifically directed into the reductase branch of the LOX pathway leading mainly to the accumulation of (13S,9Z,11E,15Z)‐13‐hydroxy‐9,11,15‐octadecatrienoic acid (13‐HOT). Under these conditions, no accumulation of other products of the LOX pathway has been found. Moreover, exogenously applied 13‐HOT led to PR1b expression suggesting for the time a role of hydroxy polyenoic fatty acid derivatives in plant defense reactions.
Conservative surgery for ovarian cancer and effect on fertility
Authors: Gonzalez‐Lira G. , Ríos P. Escudero‐De Los , Salazar‐Martínez E. , Lazcano‐Ponce E.G.
Published: July 2002

Objective: A survey that compared two alternatives (conservative and radical surgery) is presented on ovarian cancer treatment evaluating its effect on progression‐free survival and fertility, in a 10‐year time period, in Mexican women. Methods: 72 women between 11 and 58 years old with unilateral ovarian cancer in different stages were studied. Several methods were analyzed: (1) progression‐free survival, using Mantel and Haenzsel test to compare in terms of life curves and the Kaplan‐Meier method. The exposure variable was surgery type, using the Mantel‐Cox test to evaluate the difference in life curves by clinical stages and by surgery type; (2) fertility was evaluated in women who received conservative surgery, considering the cumulative pregnancy rate in women successfully pregnant after surgical and/or adjuvant treatment. Results: There were no differences in survival curves when evaluating progression‐free survival, in either group (Z = 1.09 and Pr > (z) = 0.27). During the study period, we found that 87.5% of patients were alive with no evidence of disease. There were no differences in survival curves when evaluating progression‐free survival according to surgery type and clinical stage (χ2 = 0.66, P = 0.88). Restart of menstruation in patients with conservative surgery occurred before 6 months in 89% of the sample, 22 women with possible parity had a 59.1% cumulative pregnancy rate. Conclusions: The outcomes from this survey carried out in Mexico show that conservative treatment of ovarian cancer in early clinical stages is an efficient alternative to preserve reproductive function in young women, and does not show differences in progression‐free survival compared to radical surgery.
RINGO efficiently triggers meiosis resumption in mouse oocytes and induces cell cycle arrest in embryos
Authors: Terret Marie‐Emilie , Ferby Ingvar , Nebreda Angel R. , Verlhac Marie‐Hélène
Published: July 2002

Summry— RINGO was identified as a Cdc2‐binding and activating protein which is necessary and sufficient to trigger G2/M progression in Xenopus oocytes. We have investigated whether the function of RINGO is conserved in mouse oocytes. We show that RINGO induces Germinal Vesicle BreakDown (GBVD) in mouse oocytes. Mos is known to induce GVBD in mouse oocytes, and is also involved in the metaphase II arrest, which is due to the CSF (CytoStatic Factor) activity. We found that RINGO also has CSF activity and induces cleavage arrest after injection into one blastomere of a late two‐cell mouse embryo, like Mos. However, RINGO also inhibits polar body extrusion of wild type mouse oocytes. The same effect of RINGO on first and second polar body extrusion was observed in Mos‐ /‐ mouse oocytes. The injection of RINGO mimics Mos effects: GVBD induction and efficient cleavage arrest. However, our results in mouse oocytes suggest that RINGO  may have additional functions in meiosis regulation.
Temporal expression of nitric oxide synthase isoforms in healing Achilles tendon
Authors: Lin Jian‐Hao , Wang Min‐Xia , Wei Aiqun , Zhu Wei , Diwan Ashish D. , Murrell George A. C.
Published: July 2002

We investigated the temporal expressions of the three nitric oxide synthase (NOS) isoforms by semi‐quantitative polymerase chain reaction (PCR) assays and by immunoblot analysis, following Achilles tendon transection in rats. Four days after injury, there were increases in the steady‐state levels of mRNA for all three NOS isoforms, with peaks for the inducible isoform (iNOS) (23‐fold increase) at day 4, the endothelial isoform (eNOS) (24‐fold increase) at day 7 and the neuronal isoform (bNOS) (seven‐fold increase) at day 21. The temporal expression of NOS isoforms at a protein level was consistent with the results at the mRNA level. We have previously shown a five‐fold increase in the NOS activity, as detected by 3H‐arginine to 3H‐citrulline conversion, at day 7 postinjury. These findings indicate that all three NOS isoforms are expressed during tendon healing with differential expression patterns during the various phases of tendon healing. These findings may prove clinically relevant with respect to strategies for regulating tendon healing. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Effects of oxidative stress on prion protein expression in pc12 cells
Authors: Brown David R. , Schmidt Bernhard , Kretzschmar Hans.A.
Published: July 2002

PC12 cells are known to express the prion protein, a normal cell surface glycoprotein. This protein is upregulated in PC12 cells differentiated with nerve growth factor. A neurotoxic prion protein peptide, PrP106‐126, is not toxic to PC12 cells alone. PrP106‐126 is toxic to PC12 cells co‐cultured with microglia and more so to NGF‐differentiated PC12 cells. PC12 cells selected for resistance to either copper toxicity or oxidative stress have higher levels of PrPC expression. Both PC12 variants are more sensitive to the toxicity of PrP106‐126. This suggests that PC12 sensitivity to PrP106‐126 toxicity is related to prion protein expression and not to a state of high differentiation induced by NGF. Variants of PC12 cells that are more resistant to copper toxicity have higher levels of anti‐oxidant enzymes, superoxide dismutase and glutathione peroxidase. Our results suggest that cells expressing higher levels of PrPC have higher resistance to oxidative stress or copper toxicity but are more sensitive to PrP106‐126 toxicity. Prion protein expression may be involved in both the metabolism of copper and resistance to oxidative stress. Increased cellular resistance to copper toxicity may be partly related to increased activity of anti‐oxidant enzymes. © 1997 ISDN. Published by Elsevier Science Ltd.
Effects of amyloid precursor protein derivatives andoxidative stress on basal forebrain cholinergic systems inALZHEIMERS disease
Authors: Mattson Mark P. , Pedersen Ward A.
Published: July 2002

The dysfunction and degeneration of cholinergic neuronal circuits in the brain is aprominent feature of Alzheimers disease. Increasing data suggest that age‐related oxidative stresscontributes to degenerative changes in basal forebrain cholinergic systems. Experimental studieshave shown that oxidative stress, and membrane lipid peroxidation in particular, can disruptmuscarinic cholinergic signaling by impairing coupling of receptors to GTP‐binding proteins.Altered proteolytic processing of the β‐amyloid precursor protein (APP) may contributeto impaired cholinergic signaling and neuronal degeneration in at least two ways. First, levels ofcytotoxic forms of amyloid β‐peptide (Aβ) are increased ; Aβdamages and kills neurons by inducing membrane lipid peroxidation resulting in impairment ofion‐motive ATPases, and glucose and glutamate transporters, thereby rendering neuronsvulnerable to excitotoxicity. The latter actions of Aβ may be mediated by4‐hydroxynonenal, an aldehydic product of membrane lipid peroxidation that covalently modifiesand inactivates the various transporter proteins. Subtoxic levels of Aβ can also suppresscholine acetyltransferase levels, and may thereby promote dysfunction of intact cholinergiccircuits. A second way in which altered APP processing may endanger cholinergic neurons is byreducing levels of a secreted form of APP which has been shown to modulate neuronalexcitability, and to protect neurons against excitotoxic, metabolic and oxidative insults. Mutationsin presenilin genes, which are causally linked to many cases of early‐onset inherited Alzheimersdisease, may increase vulnerability of cholinergic neurons to apoptosis. The underlying mechanismappears to involve perturbed calcium regulation in the endoplasmic reticulum, which promotesloss of cellular calcium homeostasis, mitochondrial dysfunction and oxyradical production.Knowledge of the cellular and molecular underpinnings of dysfunction and degeneration ofcholinergic circuits is leading to the development of novel preventative and therapeuticapproaches for Alzheimers disease and related disorders.
Relationships between antisocial personality and alcoholism: genetic hypotheses
Authors: Limosin F. , Adès J. , Gorwood P.
Published: July 2002

Genetic factors explain a non-negligible part of the vulnerability to alcohol dependence, the genetic influence in males being estimated at around 60%. The search for gene(s) potentially implicated in alcoholism is counteracted by the clinical heterogeneity of alcoholism, but also by heterogeneity of the etiologic factors involved. It is thus necessary to redefine more specific phenotypes with more simple determinism, and to focus on more specific subsets of candidate genes. In this view, the existence of co-occurrence (presence at the same time, whatever the cause) between antisocial personality and alcoholism is frequently reported. Three hypotheses have been previously proposed to explain this co-occurrence. Firstly, it could be a pure artefact or contamination, due to common items in diagnostic manuals widely used, such as the DSM or ICD. Secondly, antisocial personality and alcoholism could share common etiologic factor(s), and determine a ‘real’ co-morbidity. Finally, common genetic factors between these two disorders may exist, with the observation of a co-transmission of both disorders more often than expected by chance alone, meaning the existence of co-aggregation. Each of these three hypotheses will be reviewed and discussed.
Altered baroreflex gain during voluntary breathing in chronic heart failure
Authors: Mangin L. , Monti A. , Médigue C. , Macquin‐Mavier I. , Lopes M.‐E. , Gueret P. , Castaigne A. , Swynghedauw B. , Mansier P.
Published: July 2002

Background:

We assessed the behavior of the baroreflex (BR) gain in chronic heart failure (CHF) patients using the spectral analysis method during application of a forcing stimulus, i.e. respiration.

Methods:

Simultaneous RR interval and arterial pressure fluctuation recordings were obtained during two random‐order periods of voluntary paced‐breathing (0.15 Hz and 0.25 Hz) in seven patients with moderate CHF (NYHA class II/III; EF, 30 ± 9%; peak VO2, 18 ± 5 ml kg−1 min−1) and six age‐matched controls. BR gain was assessed in the time (sequential method) and frequency (cross‐spectral gain in the low and high frequency) domains.

Results:

Slower breathing was associated with a BR gain decrease in CHF patients whereas a BR gain increase was evidenced in controls (BR gain: 6 ± 5 ms mmHg−1 at 0.25 Hz vs. 4 ± 3 ms mmHg−1 at 0.15 Hz, P < 0.05 in CHF; BR gain: 12 ± 7 ms mmHg−1 at 0.25 Hz vs. 15 ± 7 ms mmHg−1 at 0.15 Hz, P < 0.05 in controls).

Conclusions:

Voluntary breathing, which involves cortical centers in the brain, had major effects on cardiovascular system controller gain in CHF patients, indicating an impairment of the central neural regulation of the autonomic outflow.
Abnormal contractile responses during dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy
Authors: Richard M. de Jong , Jan H. Cornel , Harry J.G.M. Crijns , van Veldhuisen Dirk J.
Published: July 2002

Background:

In chronic heart failure augmented wall stress leads to increased energy demand. Supply, however, may be reduced due to coronary vasoconstriction and endothelial dysfunction. This might lead to a mismatch between demand and supply. In the present study we further explored the effect of increased demand during dobutamine stress echocardiography.

Methods and results:

Sixteen patients with idiopathic dilated cardiomyopathy (mean age 44±13 years, New York Heart Association class II–III, mean left ventricular ejection fraction 0.27±0.10) underwent dobutamine stress echocardiography (5–40 μg/min per kg bodyweight+atropine if required). Wall motion and thickening was assessed in 16 segments using a four‐point scale. Eleven patients (69%) showed regions with worsening of wall motion or a biphasic response during dobutamine infusion. Of the remaining five patients one patient did not show any wall motion changes and one patient showed a partial improvement while only in three patients wall motion improvement in the whole heart was found.

Conclusion:

A majority of patients with idiopathic dilated cardiomyopathy showed decreased wall motion during increased demand, i.e. ischemia‐like myocardial contractile responses during dobutamine stress echocardiography. These findings further support the concept that an energy mismatch between demand and supply might play a pathophysiological role in idiopathic dilated cardiomyopathy.
Antiparasitic Efficacy of Crude Plant Extracts and Compounds Purified from Plants against the Fish Monogenean Neobenedenia girellae
Authors: Liu Hui-Ru , Liu Yan-Meng , Hou Ting-Long , Li Chun-Tao , Zhang Qi-Zhong
Published: April 2021

Neobenedenia girellae is a pathogenic ectoparasite of many marine fishes, and it causes major epidemics in marine aquaculture. In this study, the efficacy of ethanol extracts of huangqi Astragalus membranaceus (known as milkvetch in North America), guanzhong Dryopteris setosa (known as beaded wood fern in North America), gancao Glycyrrhiza uralensis (known as Chinese licorice in North America), danshen Salvia  miltiorrhiza (known as red sage in North America), and pomegranate Punica granatum, as well as seven phytochemicals (10-gingerol, curcumin, cynatratoside-C, emodin, kuwanon-G, kuwanon-O, and sophoraflavanone-G), against adult N. girellae was investigated. In vitro results indicated that pomegranate extract killed all adult N. girellae at a 62.5-mg/L concentration with an 8-h exposure, but gancao extract did not cause 100% mortality until a 1,000-mg/L concentration was used. Additionally, all adult N. girellae died after an 8-h exposure to cynatratoside-C, kuwanon-G, kuwanon-O, or sophoraflavanone-G at a concentration of 125 mg/L. Curcumin, emodin, and 10-gingerol at a concentration of 1,000 mg/L did not kill all parasites after an 8-h exposure. These findings demonstrate that plant extracts and active phytochemicals are potential sources of botanical drugs for controlling N. girellae infection in aquaculture.
Improving Image‐Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen
Authors: Jiang Ruming , Dai Jun , Dong Xiaoqi , Wang Quan , Meng Zijuan , Guo Jingjing , Yu Yongjiang , Wang Shixuan , Xia Fan , Zhao Zujin , Lou Xiaoding , Tang Ben Zhong
Published: April 2021

Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation‐induced‐emission luminogen (AIEgen), DDTB, is designed to integrate near‐infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen‐based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image‐guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles‐mediated photothermal/photodynamic therapy plus programmed death‐ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.
Absolute Quantification of Drug Vector Delivery to the Cytosol
Authors: Lucchino Marco , Billet Anne , Bai Siau‐Kun , Dransart Estelle , Hadjerci Justine , Schmidt Frédéric , Wunder Christian , Johannes Ludger
Published: April 2021

Macromolecular drugs inefficiently cross membranes to reach their cytosolic targets. They require drug delivery vectors to facilitate their translocation across the plasma membrane or escape from endosomes. Optimization of these vectors has however been hindered by the difficulty to accurately measure cytosolic arrival. We have developed an exceptionally sensitive and robust assay for the relative or absolute quantification of this step. The assay is based on benzylguanine and biotin modifications on a drug delivery vector of interest, which allow, respectively, for selective covalent capture in the cytosol with a SNAP‐tag fusion protein and for quantification at picomolar sensitivity. The assay was validated by determining the absolute numbers of cytosolic molecules for two drug delivery vectors: the B‐subunit of Shiga toxin and the cell‐penetrating peptide TAT. We expect this assay to favor delivery vector optimization and the understanding of the enigmatic translocation process.
Atomic Tungsten on Graphene with Unique Coordination Enabling Kinetically Boosted Lithium–Sulfur Batteries
Authors: Wang Peng , Xi Baojuan , Zhang Zhengchunyu , Huang Man , Feng Jinkui , Xiong Shenglin
Published: April 2021

Use of catalytic materials is regarded as the most desirable strategy to cope with sluggish kinetics of lithium polysulfides (LiPSs) transformation and severe shuttle effect in lithium–sulfur batteries (LSBs). Single‐atom catalysts (SACs) with 100 % atom‐utilization are advantagous in serving as anchoring and electrocatalytic centers for LiPSs. Herein, a novel kind of tungsten (W) SAC immobilized on nitrogen‐doped graphene (W/NG) with a unique W‐O2N2‐C coordination configuration and a high W loading of 8.6 wt % is proposed by a self‐template and self‐reduction strategy. The local coordination environment of W atom endows the W/NG with elevated LiPSs adsorption ability and catalytic activity. LSBs equipped with W/NG modified separator manifest greatly improved electrochemical performances with high cycling stability over 1000 cycles and ultrahigh rate capability. It indicates high areal capacity of 6.24 mAh cm−2 with robust cycling life at a high sulfur mass loading of 8.3 mg cm−2.
Innervation of the wrist joint: Literature review and clinical implications
Authors: Bonczar Tomasz , Bonczar Mariusz , Pękala Jakub R. , Mann Mitchell R. , Walocha Jerzy A.
Published: April 2021

The aim of this study was to review the literature on the innervation of the wrist with an emphasis on pathological and therapeutic aspects. The nerves involved in wrist innervation and their mechanoreceptor endings are described. The literature over the past 30 years includes several topics that are still subjects of discussion and debate and require further research.
Baohuoside I Inhibits the Proliferation of Hepatocellular Carcinoma Cells via Apoptosis Signaling and NF‐kB Pathway
Authors: Sun Yunlong , Pang Bo , Wang Yingzhe , Xiao Jinglei , Jiang Dacheng
Published: April 2021

Baohuoside I is a flavonoid isolated from Epimedium koreanum Nakai and has many pharmacological activities. However, its role in liver cancer remains unclear. This study aimed to investigate the inhibitory effect of Baohuoside I on the Human Hepatocellular Carcinoma (HCC) cell lines QGY7703, and underlying mechanisms. QGY7703 cells were used as the model to assess the function of Baohuoside I in vitro. The effects of Baohuoside I on QGY7703 cells’ growth, proliferation, and invasiveness were confirmed by CCK‐8, lactate dehydrogenase release, and invasion assays. Cell apoptosis was analyzed by flow cytometry, and the levels of cleaved Caspase‐3, Bax, and Bcl‐2 were quantified by western blot. Western blot analysis, nuclear translocation of NF‐κB, and Q‐PCR were used to measure the expression of affected molecules. In QGY7703 cells, Baohuoside I induced the expression of molecules related to NF‐κB pathway. The toxicity of Baohuoside I on QGY7703 cells was also confirmed in vivo, in a tumor model. Baohuoside I had a significant toxic effect on QGY7703 cells from a concentration of 10 μM. This compound significantly inhibited the proliferation of QGY7703 cells by inducing apoptosis and downregulating NF‐κB signaling pathway. Thus, Baohuoside I is a novel candidate drug and opens new possibilities of clinical strategies for HCC treatment.
Synthesis of Semi‐Aromatic Di‐Block Polyesters by Terpolymerization of Macrolactones, Epoxides, and Anhydrides
Authors: D'Auria Ilaria , Santulli Federica , Ciccone Francesca , Giannattasio Alessia , Mazzeo Mina , Pappalardo Daniela
Published: April 2021

In this contribution, the catalytic behavior of a phenoxy‐imine aluminum catalyst and of a bimetallic salen aluminum complex in ring‐opening polymerization (ROP) of macrolactones such as ω‐pentadecalactone (PDL), ω‐6‐hexadecenlactone (HDL) and ethylene brassylate (EB), and in the ring‐opening copolymerization (ROCOP) of cyclohexene oxide (CHO) and phthalic anhydride (PA) is described. A significant difference in terms of activity emerged between the two catalysts in the ROP of the macrolactones, while similar behaviors were observed in the ROCOP process. The synthesis of diblock polyesters, by combination of two distinct processes, was performed in a one‐pot procedure. The semi‐aromatic polyester block was formed first, followed by the polyethylene‐like portion produced by ROP of macrolactones.
Tetra‐Heteroatom‐Doped Ultra‐Mesoporous Carbon from Polyphosphazene for High‐Performance Supercapacitors
Authors: Qiu Munan , Zhang Shuangkun , Li Min , Abbas Yasir , Yang Fan , Miao Zhenwei , Liu Wei , Qi Shengli , Wu Zhanpeng
Published: April 2021

Applying multi‐heteroatoms doping strategy to prepare porous carbon materials with high surface area has been demonstrated to be effective for enhancing electrochemical performance of supercapacitors. In this study, N, P, O, and Si tetra‐atoms‐doped hierarchically micro‐/mesoporous carbon with ultrahigh surface area is fabricated from crosslinked‐linear poly(diaryloxyphosphazene) precursor by using silica which serves as both template and dopant. The surface area and heteroatoms doping content of the synthesized carbons are tailored by tuning silica dosage and carbonization temperature. The tetra‐atoms‐doped mesoporous carbon exhibits an ultrahigh surface area of 3,132 m2/g with enriched heteroatoms content (22 at%), which contribute to the capacitive performance. The as‐fabricated tetra‐atoms‐doped carbon symmetric cell displays outstanding specific capacitance of 288.8 F/g (0.5 A/g) (539.8 F/g in three‐electrode system) with high remaining capacitance of 226.1 F/g at 10 A/g and excellent cycling stability (97.7 % capacity retention after 5,000 cycles at 10 A/g). This study suggests an effective multi‐heteroatoms‐doping approach to synthesize mesoporous carbon materials for high performance electrochemical conversion and storage devices.
An enhanced authentication scheme for Internet of Things and cloud based on elliptic curve cryptography
Authors: Bhuarya Pallavi , Chandrakar Preeti , Ali Rifaqat , Sharaff Aakanksha
Published: April 2021

Authentication plays a fundamental role in achieving security over unreliable channels. Authentication is a technique that lets an entity verify the identity of other communicating entities. There are a plethora of authentication schemes available in recent times. A short time ago, Kumari et al. offered an authentication protocol using elliptic curve cryptography (ECC) for Internet of Things (IoT) and professed that their design defends various security attacks. We examined Kumari et al.'s scheme and detected some loopholes like (1) inefficient login phase, (2) inefficient authentication phase, (3) known session‐specific temporary information attack, (4) denial‐of‐service (DoS) attack, and (5) lack of password changing phase. To eradicate all these flaws, we present an enhanced authentication protocol utilizing ECC for deployment in the field of IoT using cloud servers. This protocol uses hypertext transfer protocol (HTTP) cookies to authenticate clients. The developed protocol provides various security features and able to counter various security attacks. The security analysis validates that the extended scheme is potent. We simulate our protocol in Automated Validation of Internet Security Protocols and Applications (AVISPA) tool that evaluates the safety of the scheme in the presence of an adversary. We compare the proposed scheme with some similar schemes in respect of computation cost, estimated time, storage cost, communication cost, and security features.
Review on Microphotosynthetic Power Cells—A Low‐Power Energy‐Harvesting Bioelectrochemical Cell: From Fundamentals to Applications
Authors: Kuruvinashetti Kiran , Tanneru Hemanth Kumar , Pillay Pragasen , Packirisamy Muthukumaran
Published: April 2021

Biophotoelectrochemical cells are gaining prominence in recent years due to the necessity of sustainable power generation at both micro‐ and macroscale. Toward this direction, microphotosynthetic power cells (μ‐PSC) play a vital role in generating clean energy. The μ‐PSC generates sustainable power under light and in the dark through the photosynthesis and respiration of photosynthetic microorganisms or cells, such as cyanobacteria and green algae. Herein, particulars on μ‐PSCs from fundamentals to real‐time applications are provided. The state of the art of μ‐PSCs, in terms of the principle of operation, design, and materials is presented. μ‐PSCs reported to date are classified based on design, operating parameters, and photosynthetic organisms. In addition, details on the metrics and factors influencing the performance of μ‐PSCs are also discussed. The need for the development of mathematical and electrical equivalent models of μ‐PSCs and the progress in these areas are briefed. Current challenges for μ‐PSCs’ commercialization are identified as high cost and low power densities, and the factors that are leading to low power density and high cost are explored and are also discussed. In addition, the potential solutions to overcome these challenges are investigated.
Effects of Electrolyte Additives and Nanowire Diameter on the Electrochemical Performance of Lithium‐Ion Battery Anodes based on Interconnected Nickel–Tin Nanowire Networks
Authors: Omale Joel O. , Van Velthem Pascal , Antohe Vlad-Andrei , Vlad Alexandru , Piraux Luc
Published: April 2021

Tin‐based nanowire electrodes present desirable properties as lithium‐ion battery anodes, because they undergo volume changes without pulverization. However, they suffer from limited mass loading and propensity for surface parasitic reactions. Herein, the electrochemical performances of nickel–tin 3D‐interconnected nanowire network (NiSn 3DNWN) electrodes are evaluated with the nanowire diameters of 40, 105, and 230 nm, respectively, that attain mass loadings of up to 3 mg cm−2. To mitigate the surface parasitic reactions, the effects of fluoroethylene carbonate (FEC) and vinylene carbonate (VC) additives are investigated as a function of the nanowire diameter and additive concentration. The results show that the FEC and VC of all compositions improve the capacity retentions and coulombic efficiencies (CEs) of the NiSn 3DNWN electrodes. In 10 vol% FEC, the electrodes demonstrate a similar capacity of ≈550 mAh g−1, but the capacity retentions after 100 cycles are 73.68%, 53.79%, and 51.70% for the 40, 105, and 230 nm NiSn 3DNWN, respectively. However, the 105 nm‐diameter nanowire electrode has the highest average CE of 96.55%. Electrochemical impedance spectroscopy and post‐cycling investigations reveal that the FEC has the most profound effect on the interfacial resistances, which is reflected in the rate performances of the tested electrodes.