bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a D1‐D2‐cyt b‐559 complex containing 4 chlorophyll a/2 pheophytin a isolated with the use of MgSO4
Authors: Yruela I. , van Kan P.J.M. , Müller M.G. , Holzwarth A.R.
Published: July 2002

A D1‐D2‐cyt b‐559 complex containing 4 chlorophyll a, 1 β‐carotene and 1 cytochrome b‐559 per 2 pheophytin a has been isolated from spinach with 30% yield using a Q‐Sepharose Fast‐Flow anion‐exchange column equilibrated with 0.1% Triton X‐100, 10 mM MgSO4 and 50 mM Tris‐HCl (pH 7.2). The preparation was then stabilized with 0.1% dodecyl‐β‐d‐maltoside. This method gave a yield 10 times higher than that using a Fractogel TSK‐DEAE 650(S) column equilibrated with 0.1% Triton X‐100, 30 mM NaCl and 50 mM Tris‐HCl (pH 7.2). The PS II RC complex was characterized using absorption and fluorescence spectroscopy at 277 and 77 K. A selective reversible bleaching under reducing conditions with maximum at 682 nm, associated with pheophytin a reduction, and light‐induced absorption differences with a lifetime of 1.0 ms, ascribed to the triplet state of P680 were measured and indicated that the isolated Dl‐D2‐cyt b‐559 complex is active in charge separation. The results are compared with the data obtained for a PS II RC preparation containing 6 chlorophyll a, 2 β‐carotene and 1 cyt b‐559 per 2 pheophytin a.
Inhibition of cruzipain, the major cysteine proteinase of the protozoan parasite, Trypanosoma cruzi, by proteinase inhibitors of the cystatin superfamily
Authors: Stoka Veronika , Nycander Maria , Lenarčič Brigita , Labriola Carlos , Cazzulo Juan José , Björk Ingemar , Turk Vito
Published: July 2002

Cruzipain, the major cysteine proteinase from Trypanosoma cruzi epimastigotes, purified to a sequentially pure form, exists in multiple forms with pI values between 3.7 and 5.1, and an apparent molecular mass of 41 kDa. The enzyme is stable between pH 4.5–9.5. Cruzipain was found to be rapidly and tightly inhibited by various protein inhibitors of the cystatin superfamily (k
ass = 1.7–79 × 106M−1s−1, K
d = 1.4–72 pM). These results suggest a possible defensive role for the host's cystatins after parasite infection, and may be of use for the design of new therapeutic drugs.
Does community-based care have an effect on public attitudes toward the mentally ill?
Authors: Rössler W , Salize HJ , Voges B
Published: July 2002

In this cross-sectional study we have investigated the attitudes and feelings toward the mentally ill among the residents of two Central European regions which are at considerably different stages of development in moving toward community-based care, to see if we could connect differing patterns of attitudes in the two regions to the varying levels of development of psychiatric care. By using the telephone survey method, representative samples of interviewees were presented with two complexes of questions, measuring the social distance of the interviewee to the mentally ill and his/her feelings toward the mentally ill. Social rejection and feelings of the people toward the mentally ill in both regions were similar in the direction they took, however not so much in the intensity. The population of the community care area showed a slightly stronger rejection. But factor analysis clearly suggests a more rational and sophisticated position toward the patients in this population. The people living in the custodially-oriented catchment area, on the other hand, showed a more vague pattern in their attitudes.
Functional and possible physical association of scavenger receptor with cytoplasmic tyrosine kinase Lyn in monocytic THP‐1‐derived macrophages
Authors: Miki Shunji , Tsukada Satoshi , Nakamura Yu , Aimoto Saburo , Hojo Hironobu , Sato Bunzo , Yamamoto Masahiro , Miki Yoshitsugu
Published: July 2002

Acetyl LDL (modified low‐density lipoprotein), which is thought to be taken up through scavenger receptor A (SR‐A), rapidly induced the appearance of phosphotyrosine proteins in monocytic THP‐1‐derived macrophages in vitro. The two alternative forms of Lyn (p53 and p56) were found to be tyrosine‐phosphorylated within 30 s after the stimulation with acetyl LDL. The catalytic activity of Lyn measured by an in vitro kinase assay had also increased in acetyl LDL‐stimulated THP‐1‐derived macrophages. Furthermore, Lyn could be co‐immunoprecipitated with SR‐A from the cell lysate. These observations suggest a functional and possible physical association of SR‐A with Lyn in THP‐1‐derived macrophages, and also imply a possible involvement of Lyn in SR‐A signal transduction.
Sequence of subunit c of the Na+‐translocating F1FO ATPase of Acetobacterium woodii: proposal for determinants of Na+ specificity as revealed by sequence comparisons
Authors: Rahlfs Stefan , Müller Volker
Published: July 2002

© 1997 Federation of European Biochemical Societies.
Inactive fatty acids are unable to flip‐flop across the lipid bilayer
Authors: Ježek Petr , Modrianský Martin , Garlid Keith D
Published: July 2002

Free fatty acids (FA) were found which did not acidify liposome interior. This is interpreted as their inability to rapidly flip‐flop across the lipid bilayer. However, they were able to partition in lipids as detected directly using HPLC or from the shift of their equilibrium binding to acrylodated intestinal binding protein (ADIFAB) in the presence of vesicles. Various bipolar FA, such as 12‐hydroxylauric acid, dicarboxylic acids, or FA with benzene ring at the tail were found to be inactive in this way. A phenomenon of shielding, where an additional alkyl chain or non‐polar group can restore the flip‐flop activity, is described.
Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non‐synaptic mitochondria of aged rats
Authors: Luisa Genova Maria , Bovina Carla , Marchetti Mario , Pallotti Francesco , Tietz Catleen , Biagini Graziella , Pugnaloni Armanda , Viticchi Claudio , Gorini Antonella , Federico Villa Roberto , Lenaz Giorgio
Published: July 2002

We investigated NADH oxidation in non‐synaptic and synaptic mitochondria from brain cortex of 4‐ and 24‐month‐old rats. The NADH oxidase activity was significantly lower in non‐synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone‐binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.
Cytochrome P450IA2 and aromatic l‐amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I
Authors: Gebre-Medhin G , Husebye E.S , Gustafsson J , Winqvist O , Goksøyr A , Rorsman F , Kämpe O
Published: July 2002

Autoimmune chronic active hepatitis (AI‐CAH) is a feared component of autoimmune polyendocrine syndrome type I (APS I). In this study, immunoreactivity was assessed in sera from eight APS I patients, of whom three had AI‐CAH, in an attempt to identify hepatic autoantigens. We performed indirect immunofluorescence staining of human and rat liver sections, Western blots on subcellular fractions of human and rat liver, immunoprecipitations of labelled aromatic l‐amino acid decarboxylase (AADC) and cytochrome P450IA2 (CYP IA2) expressed by an in vitro transcription and translation system and studies of enzymatic activity. Autoantibodies against AADC were present in sera from all eight APS I patients, while immunoreactivity against CYP IA2 was only found in sera from the three APS I patients with AI‐CAH. Enzymatic activity of CYP IA2 was inhibited by sera from APS I patients with AI‐CAH but not by control sera. Our results show that CYP IA2 and AADC constitute hepatic autoantigens in patients with APS I and that immunoreactivity against CYP IA2 is associated with the presence of AI‐CAH.
Preparation of peptides which mimic glycosphingolipids by using phage peptide library and their modulation on β‐galactosidase activity
Authors: Taki Takao , Ishikawa Dai , Hamasaki Hiroko , Handa Shizuo
Published: July 2002

We describe the use of a phage‐displayed random pentadecamer peptide library for searching glycosphingolipid mimicking peptides. Two phage clones (AD‐1 and AD‐2) were selected by biopanning using monoclonal antibody AD117m, directed to lactotetraosylceramide (Lc4Cer). The amino acid sequences of the selected clones showed high homology (VPPXFXXXY) in 9‐mer. Three phage clones were selected by using monoclonal antibody H11, directed to neolactotetraosylceramide (nLc4Cer), the linkage isomer of Lc4Cer, and the displayed amino acid sequences were compared. One of these peptides showed the same amino acid sequence as that of AD‐2 except for one amino acid substitution. Pentadecamer, 9‐mer and point mutated 9‐mer peptides were synthesized on the basis of the displayed amino acid sequences. Binding activity of the peptides to the monoclonal antibodies or Ricinus communis lectin showed that 9‐mer peptides are enough to mimic the epitope carbohydrate structure. Furthermore, six of the synthesized peptides inhibited Jack bean β‐galactosidase activity towards nLc4Cer at a high concentration of the enzyme, whereas at lower enzyme concentrations some peptides showed potent activation of the enzyme activity. This is the first report of carbohydrate mimicking peptides which modulate glycosidase activity.
Formation of a dihydropyridine derivative as a potential cross‐link derived from malondialdehyde in physiological systems
Authors: Slatter David A , Murray Martin , Bailey Allen J
Published: July 2002

Malondialdehyde is a major oxidation product of lipids which is capable of cross‐linking the collagen of the cardiovascular system. Identification of cross‐links usually involves degradative procedures. In this paper, we use a novel, direct, approach using nuclear magnetic resonance to identify early and labile products. Initial model studies show that malondialdehyde reacts with lysine to form a dihydropyridine derivative rather than the unstable imidopropene Schiff base previously reported. The aldehydes on the pyridine ring could react further to cross‐link collagen and stiffen the aorta, thereby promoting further glycation, a process that would be accelerated in diabetes.
Anti‐digoxin scFv fragments expressed in bacteria and in insect cells have different antigen binding properties
Authors: Lemeulle Corinne , Chardès Thierry , Montavon Céline , Chaabihi Hassan , Mani Jean-Claude , Pugnière Martine , Cerutti Martine , Devauchelle Gérard , Pau Bernard , Biard-Piechaczyk Martine
Published: July 2002

A gene encoding a single‐chain antibody fragment directed against digoxin (named 1C10 scFv) was cloned in two expression systems. For this purpose, a new baculovirus transfer cassette fully compatible with the procaryotic pHEN vector was constructed. Baculovirus production led to higher yield than did Escherichia coli expression. The procaryotic fragment showed variations in the fine specificity profile but an affinity constant nearly identical to that of the 1C10 Fab, whereas the eucaryotic scFv fragment had a lower affinity with a specificity profile identical to original mAb. The half‐lives of the digoxin:scFv complexes and the global specificity are compatible with therapeutic use of this antibody fragment.
α‐Glucosidase inhibitors as potential broad based anti‐viral agents
Authors: Mehta Anand , Zitzmann Nicole , Rudd Pauline M , Block Timothy M , Dwek Raymond A
Published: July 2002

N‐Linked oligosaccharides play many roles in the fate and functions of glycoproteins. One function is to assist in the folding of proteins by mediating interactions of the lectin‐like chaperone proteins calnexin and calreticulin with nascent glycoproteins. These interactions can be prevented by inhibitors of the α‐glucosidases and this causes some proteins to be misfolded and retained within the endoplasmic reticulum. In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) the misfolding of key viral envelope glycoproteins interferes with the viral life cycle. It has been demonstrated in an animal model of chronic HBV that glucosidase inhibitors can alter glycosylation and have anti‐viral activity. As the mechanism of action of α‐glucosidase inhibitors is the induction of misfolded or otherwise defective viral glycoproteins, such inhibitors may be useful therapeutics for many viruses, especially those which bud from the endoplasmic reticulum (where protein folding takes place). For example bovine viral diarrhea virus, a pestivirus akin to hepatitis C virus, is also extremely sensitive to glucosidase inhibition.
Identification of multispecific organic anion transporter 2 expressed predominantly in the liver
Authors: Sekine Takashi , Cha Seok Ho , Tsuda Minoru , Apiwattanakul Nopporn , Nakajima Noriko , Kanai Yoshikatsu , Endou Hitoshi
Published: July 2002

In the present study, we demonstrate that NLT (novel liver‐specific transport protein) is a multispecific organic anion transporter of the liver. The amino acid sequence of NLT shows 42% identity to that of the renal multispecific organic anion transporter, OAT1. When expressed in Xenopus laevis oocytes, NLT mediated uptake of organic anions, such as salicylate, acetylsalicylate, PGE2, dicarboxylates and p‐aminohippurate. [14C]Salicylate uptake via NLT was saturable (K
m=88.8±23.4 μM) and sodium‐independent. Expression of the mRNA of NLT was detected in the liver and kidney (liver≫kidney). We propose that NLT be renamed OAT2.
Decelerated degradation of short peptides by the 20S proteasome
Authors: Dolenc Iztok , Seemüller Erika , Baumeister Wolfgang
Published: July 2002

Based on a twelve residue master peptide comprising all five specific cleavage sites defined for the proteasome, a set of variant peptides was generated in order to probe specificity and to elucidate the mechanism which determines product size. It is shown that the rate of degradation by the 20S proteasome from Thermoplasma acidophilum depends critically on the length of the peptide substrate. Peptides of 14 residues and longer are degraded much faster than shorter peptides although the sites of cleavage remain unchanged. The decelerated degradation of peptides shorter than 14 residues explains the accumulation of products with an average length of seven to nine residues.
Interactions between synthetic vanilloids and the endogenous cannabinoid system
Authors: Di Marzo Vincenzo , Bisogno Tiziana , Melck Dominique , Ross Ruth , Brockie Heather , Stevenson Lesley , Pertwee Roger , De Petrocellis Luciano
Published: July 2002

The chemical similarity between some synthetic agonists of vanilloid receptors, such as olvanil (N‐vanillyl‐cis‐9‐octadecenoamide), and the ‘endocannabinoid’ anandamide (arachidonoyl‐ethanolamide, AEA), suggests possible interactions between the cannabinoid and vanilloid signalling systems. Here we report that olvanil is a stable and potent inhibitor of AEA facilitated transport into rat basophilic leukemia (RBL‐2H3) cells. Olvanil blocked both the uptake and the hydrolysis of [14C]AEA by intact RBL‐2H3 cells (IC50=9 μM), while capsaicin and pseudocapsaicin (N‐vanillyl‐nonanamide) were much less active. Olvanil was more potent than previously reported inhibitors of AEA facilitated transport, i.e. phloretin (IC50=80 μM), AM404 (12.9% inhibition at 10 μM) or oleoylethanolamide (27.5% inhibition at 10 μM). Olvanil was a poor inhibitor of [14C]AEA hydrolysis by RBL‐2H3 and N18TG2 cell membranes, suggesting that the inhibitory effect on [14C]AEA breakdown observed in intact cells was due to inhibition of [14C]AEA uptake. Olvanil was stable to enzymatic hydrolysis, and (i) displaced the binding of high affinity cannabinoid receptor ligands to membrane preparations from N18TG2 cells and guinea pig forebrain (Ki=1.64–7.08 μM), but not from cells expressing the CB2 cannabinoid receptor subtype; (ii) inhibited forskolin‐induced cAMP formation in intact N18TG2 cells (IC50=1.60 μM), this effect being reversed by the selective CB1 antagonist SR141716A. Pseudocapsaicin, but not capsaicin, also selectively bound to CB1 receptor‐containing membranes. These data suggest that some of the analgesic actions of olvanil may be due to its interactions with the endogenous cannabinoid system, and may lead to the design of a novel class of cannabimimetics with potential therapeutic applications as analgesics.
Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin‐3
Authors: Kim Injune , Kwak Hee Jin , Ahn Ji Eun , So June-No , Liu Mingzhu , Koh Keum Nim , Koh Gou Young
Published: July 2002

Using homology‐based PCR, we have isolated cDNA encoding a novel member (491 amino acids) of the angiopoietin (Ang) family from human adult heart cDNA and have designated it angiopoietin‐3 (Ang3). The NH2‐terminal and COOH‐terminal portions of Ang‐3 contain the characteristic coiled‐coil domain and fibrinogen‐like domain that are conserved in other known Angs. Ang3 has a highly hydrophobic region at the N‐terminus (∼21 amino acids) that is typical of a signal sequence for protein secretion. Ang3 mRNA is most abundant in adrenal gland, placenta, thyroid gland, heart and small intestine in human adult tissues. Additionally, Ang3 is a secretory protein, but is not a mitogen in endothelial cells.
Vacuolar processing enzyme is self‐catalytically activated by sequential removal of the C‐terminal and N‐terminal propeptides
Authors: Hiraiwa Nagako , Nishimura Mikio , Hara-Nishimura Ikuko
Published: July 2002

A vacuolar processing enzyme (VPE) responsible for maturation of various vacuolar proteins is synthesized as an inactive precursor. To clarify how to convert the VPE precursor into the active enzyme, we expressed point mutated VPE precursors of castor bean in the pep4 strain of Saccharomyces cerevisiae. A VPE with a substitution of the active site Cys with Gly showed no ability to convert itself into the mature form, although a wild VPE had the ability. The mutated VPE was converted by the action of the VPE that had been purified from castor bean. Substitution of the conserved Asp‐Asp at the putative cleavage site of the C‐terminal propeptide with Gly‐Gly abolished both the conversion into the mature form and the activation of the mutated VPE. In vitro assay with synthetic peptides demonstrated that a VPE exhibited activity towards Asp residues and that a VPE cleaved an Asp‐Gln bond to remove the N‐terminal propeptide. Taken together, the results indicate that the VPE is self‐catalytically maturated to be converted into the active enzyme by removal of the C‐terminal propeptide and subsequent removal of the N‐terminal one.
The neoxanthin binding site of the major light harvesting complex (LHCII) from higher plants
Authors: Croce Roberta , Remelli Rosaria , Varotto Claudio , Breton Jacques , Bassi Roberto
Published: July 2002

The localisation of the xanthophyll neoxanthin within the structure of the major light harvesting complex (LHCII) of higher plants has been investigated by site‐directed mutagenesis and spectroscopic methods. Mutation analysis performed on pigment binding sites in different helix domains leads to selective loss of neoxanthin for mutations on helix C thus localising this pigment between the helix C and helix A/B domains. Recombinant proteins binding two lutein molecules per polypeptide but lacking neoxanthin have been used in order to determine the contribution of neoxanthin to the absorption and linear dichroism spectra. The data were used to derive the orientation of the neoxanthin transition moment, lying in the polyene chain, which was thus determined to form an angle of 57±1.5° with respect to the normal to the membrane plane where the protein is inserted. On the basis of these results we propose a model for the localisation of the carotenoid site in the LHCII structure which is still unresolved.
Coordinated regulation of ceruloplasmin and metallothionein mRNA by interleukin‐1 and copper in HepG2 cells
Authors: Daffada Angela A.I , Young Stephen P
Published: July 2002

During the acute phase response, cytokines induce hepatic metallothionein and ceruloplasmin synthesis and the uptake of metals. We have investigated how copper and cytokines may interact in controlling ceruloplasmin (CP) and metallothionein mRNA in liver cells. We found that IL‐1α, IL‐1β and IL‐6 increased both metallothionein‐1 (MT‐1) and metallothionein‐2 (MT‐2) mRNA in HepG2 cells. The time and pattern of induction was different, both IL‐1α and IL‐1β inducing two peaks of MT‐1 and MT‐2, with that of MT‐2 being much larger. IL‐6 induced only low levels of both MT‐1 and MT‐2 mRNA. CP mRNA was also increased after 16 h by IL‐1β, whereas IL‐1α induced two CP peaks at 8 and 20 h, while IL‐6 had little effect. Copper administration gave rise to substantially increased MT‐1 mRNA, a slightly lower increase in MT‐2 and also a significant increase in CP mRNA with similar kinetics. These parallel increases in MT and CP mRNA suggest that the coordinated expression of these proteins may be important for their synthesis during the acute phase response.
Inhibitory mechanism of sinapinic acid against peroxynitrite‐mediated tyrosine nitration of protein in vitro
Authors: Niwa Toshio , Doi Umeyuki , Kato Yoji , Osawa Toshihiko
Published: July 2002

The peroxynitrite‐scavenging ability of some phenolic antioxidants, p‐coumaric acid, caffeic acid and sinapinic acid, was examined and compared with ascorbic acid and tocopherol using 3‐nitrotyrosine formation as a marker. Among these, caffeic acid and sinapinic acid strongly inhibited the formation of 3‐nitrotyrosine in protein. The treatment of protein with peroxynitrite in the presence of sinapinic acid, but not caffeic acid, produced a novel product determined by reversed‐phase high performance liquid chromatography (HPLC). The product formed was purified and then identified as a mono‐lactone type dimer (ML) of sinapinic acid by nuclear magnetic resonance (NMR) and liquid chromatography‐mass spectrometry (LC‐MS). This ML was converted from a di‐lactone type dimer, obtained from sinapinic acid with peroxidase/hydrogen peroxide, in neutral buffer. In this report, we have proposed that the ML of sinapinic acid is generated via one‐electron oxidation by peroxynitrite treatment.
Origin of the interferon‐inducible (2′‐5′)oligoadenylate synthetases: cloning of the (2′‐5′)oligoadenylate synthetase from the marine sponge Geodia cydonium1
Authors: Wiens Matthias , Kuusksalu Anne , Kelve Merike , Müller Werner E.G.
Published: July 2002

In vertebrates cytokines mediate innate (natural) immunity and protect them against viral infections. The cytokine interferon causes the induction of the (2′‐5′)oligoadenylate synthetase [(2‐5)A synthetase], whose product, (2′‐5′)oligoadenylate, activates the endoribonuclease L which in turn degrades (viral) RNA. Three isoforms of (2‐5)A synthetases exist, form I (40–46 kDa), form II (69 kDa), and form III (100 kDa). Until now (2‐5)A synthetases have only been cloned from birds and mammals. Here we describe the cloning of the first putative invertebrate (2‐5)A synthetase from the marine sponge Geodia cydonium. The deduced amino acid sequence shows signatures characteristic for (2‐5)A synthetases of form I. Phylogenetic analysis of the putative sponge (2‐5)A synthetase indicates that it diverged first from a common ancestor of the hitherto known members of (vertebrate) (2‐5)A synthetases I, (2‐5)A synthetases II and III. Moreover, it is suggested that the (2‐5)A synthetases II and III evolved from this common ancestor (very likely) by gene duplication. Together with earlier results on the existence of the (2′‐5′)oligoadenylates in G. cydonium, the data presented here demonstrate that also invertebrates, here sponges, are provided with the (2‐5)A system. At present, it is assumed that this system might be involved in growth control, including control of apoptosis, and acquired its additional function in innate immune response in evolutionarily younger animals, in vertebrates.
Long‐term treatment with nicardipine for severe pre‐eclampsia
Authors: Seki H , Takeda S , Kinoshita K
Published: July 2002

Objective: To evaluate the safety of long‐term nicardipine treatment in severely pre‐eclamptic women and their fetuses/newborns. Methods: We divided 50 pregnant women into three groups according to the length of their treatment: short‐term treatment of severely pre‐eclamptic women (7 days or less, n=20); medium‐term treatment also of severely pre‐eclamptic women (8–28 days, n=20); and long‐term treatment of women with severe superimposed pre‐eclampsia (29 days or more, n=10). Results: Nicardipine significantly lowered both systolic (P<0.01) and diastolic blood pressures (P<0.025) in all three groups. The incidence of delivery before 28 weeks of gestation was very low in all three groups. There were no maternal or fetal/neonatal adverse effects. Conclusion: Our results suggest that long‐term treatment with nicardipine for severe pre‐eclampsia is as effective and safe as a short‐ and medium‐term treatment.
Estrogen replacement therapy in breast cancer survivors
Authors: Guidozzi F
Published: July 2002

Objective: To determine whether estrogen replacement therapy (ERT) adversely affected outcome of breast cancer survivors. Method: A prospective descriptive study of all breast cancer survivors who requested ERT because of intractable menopausal symptoms. All patients presented voluntarily as gynecological outpatients and were all given oral continuous opposed ERT: 20 premarin and medroxyprogesterone and four tibolone. Results: Twenty‐four patients who had previously been treated for breast cancer 8–91 months prior to their initiating ERT have been observed for 24–44 months. There were 15 patients with stage 1, eight with stage 2 and one with stage 4 breast cancer. The mean age of the patients at commencement of ERT was 48 years (range 42–61). Two patients had a biopsy of a suspicious breast nodule: both of which were benign. There have not been any recurrences to date. Conclusion: Breast cancer survivors did not have their outcome adversely affected by ERT during an observation period of 24–44 months.
Supply networks and complex adaptive systems: control versus emergence
Authors: Choi Thomas Y , Dooley Kevin J , Rungtusanatham Manus
Published: July 2002

In much of the current literature on supply chain management, supply networks are recognized as a system. In this paper, we take this observation to the next level by arguing the need to recognize supply networks as acomplex adaptive system(CAS). We propose that many supply networks emerge rather than result from purposeful design by a singular entity. Most supply chain management literature emphasizes negative feedback for purposes of control; however, the emergent patterns in a supply network can much better be managed through positive feedback, which allows for autonomous action. Imposing too much control detracts from innovation and flexibility; conversely, allowing too much emergence can undermine managerial predictability and work routines. Therefore, when managing supply networks, managers must appropriately balance how much to control and how much to let emerge.
The Dorian Gray effect: winners as state breakers in postcommunism
Authors: Ganev Venelin I.
Published: July 2002

This paper examines the relations between postcommunist states and the powerful economic groups that dominated the early stages of postcommunist economic restructuring. The main argument is that the strategic actions of “winners” systematically undermine the capacity of state institutions and the organizational coherence of administrative agencies. Against the background of a detailed study of one particular story of “postcommunist success”, the rise of Multigroup in Bulgaria, I explore the concrete manifestations of “state weakness” in postcommunism, the nature of redistributive conflicts the former socialist societies, and the historical specificity of the processes undermining the organizational bases of governance in the former Soviet world.
Party identification in the Czech Republic: inter-party hostility and party preference1
Authors: Vlachová Klára
Published: July 2002

This study introduces basic models of voting behavior and describes in greater detail the findings and starting points of the model of party identification. It recapitulates findings related to the voting behavior in the Czech Republic throughout the nineties, as well as the reasons leading to the application of the party identification model to the analyses of voting behavior. The influence of positive feelings toward the elected party and negative feelings toward the other parties are tested here. The study explores in particular the influence of inter-party hostility on the voting behavior, and tests it both separately and in combination with the subjective social class and subjective political orientation.
Associations Between Baseline and Longitudinal Semiautomated Quantitative Joint Space Width at the Hip and Incident Hip Osteoarthritis: Data From a Community‐Based Cohort
Authors: Nelson Amanda E. , Smith Jacquelyn A. , Alvarez Carolina , Arbeeva Liubov , Renner Jordan B. , Murphy Louise B. , Jordan Joanne M. , Golightly Yvonne M. , Duryea Jeffrey
Published: July 2021

Objective

To evaluate quantitative joint space width (JSW) at 10‐, 30‐, and 50‐degree locations in relation to incident radiographic and symptomatic hip osteoarthritis (HOA) in a community‐based cohort.

Methods

Data were from Johnston County OA Project participants with supine hip radiographs at each of 4 time points; all had Kellgren/Lawrence (K/L) grades and quantitative JSW. We assessed covariates (age, race, height, weight, body mass index [BMI]) associated with quantitative JSW and hip‐level associations between quantitative JSW and HOA over time using sex‐stratified and multivariable‐adjusted linear mixed models. A cluster analysis with logistic regression estimated associations between quantitative JSW trajectory groups and incident radiographic HOA and symptomatic HOA.

Results

At baseline, 397 participants (784 hips, 41% men, 24% Black, mean age 57 years) had a mean BMI of 29 kg/m2. Over a mean of 18 years, 20% and 12% developed incident K/L grade–defined radiographic HOA or symptomatic HOA, respectively. Quantitative JSW was more sensitive to changes over time at 50 degrees. Values were stable among men but declined over time in women. Heavier women lost more quantitative JSW; changes in quantitative JSW were not significantly associated with race, education, or injury in women or men. In women only, loss of quantitative JSW over time was associated with 2–3 times higher odds of radiographic HOA and symptomatic HOA; among women and men, narrower baseline quantitative JSW was associated with these outcomes.

Conclusion

Hip quantitative JSW demonstrates marked differences in respect to sex, with significant loss over time only in women. Loss of quantitative JSW over time in women and narrower baseline quantitative JSW in men and women were associated with incident radiographic HOA and symptomatic HOA.
Double‐Lock Nanomedicines Enable Tumor‐Microenvironment‐Responsive Selective Antitumor Therapy
Authors: Liu Fang , Zhu Jundong , Dai Peipei , Deng Jian , Qin Juan , Yuchi Zhiguang , Fan Aiping , Wang Zheng , Zhao Yanjun
Published: July 2021

A hybrid nanocarrier for reducing the off‐target adverse effects of chemotherapy via selective drug delivery to the tumor cells is reported. The model active agent, combretastatin A4 (CA4) phosphate is deposited onto the magnetite (Fe3O4) nanoparticles as the core, followed by lipid coating as the shell. Upon nanocarrier administration and biodistribution to the tumor site, the high level of adenosine triphosphate in the extracellular space of tumor induces the cargo release via phosphate displacement. Then, the CA4 phosphate is dephosphorylated by the alkaline phosphatase that is overexpressed at the plasma membrane of certain tumor cells, resulting in enhanced intracellular uptake of hydrophobic CA4. These sequential two‐step unlocking processes enable the preferable accumulation of CA4 within tumor cells. Such approach is applicable to a wide range of chemotherapeutics and is promising for efficacy enhancement and side‐effect reduction of antitumor chemotherapy.
Shape Persistent, Highly Conductive Ionogels from Ionic Liquids Reinforced with Cellulose Nanocrystal Network
Authors: Lee Hansol , Erwin Andrew , Buxton Madeline L. , Kim Minkyu , Stryutsky Alexandr V. , Shevchenko Valery V. , Sokolov Alexei P. , Tsukruk Vladimir V.
Published: July 2021

Shape‐persistent, conductive ionogels where both mechanical strength and ionic conductivity are enhanced are developed using multiphase materials composed of cellulose nanocrystals and hyperbranched polymeric ionic liquids (PILs) as a mechanically strong supporting network matrix for ionic liquids with an interrupted ion‐conducting pathway. The integration of needlelike nanocrystals and PIL promotes the formation of multiple hydrogen bonding and electrostatic ionic interaction capacitance, resulting in the formation of interconnected networks capable of confining a high amount of ionic liquid (≈95 wt%) without losing its self‐sustained shape. The resulting nanoporous and robust ionogels possess outstanding mechanical strength with a high compressive elastic modulus (≈5.6 MPa), comparable to that of tough, rubbery materials. Surprisingly, these rigid materials preserve the high ionic conductivity of original ionic liquids (≈7.8 mS cm−1), which are distributed within and supported by the nanocrystal network‐like rigid frame. On the one hand, such stable materials possess superior ionic conductivities in comparison to traditional solid electrolytes; on the other hand, the high compression resistance and shape‐persistence allow for easy handling in comparison to traditional fluidic electrolytes. The synergistic enhancement in ion transport and solid‐like mechanical properties afforded by these ionogel materials make them intriguing candidates for sustainable electrodeless energy storage and harvesting matrices.
Molecular‐Level Contact of Graphene/Silver Nanowires through Simultaneous Dispersion for a Highly Stable Wearable Electrothermal Heater
Authors: Kwon Minho , Kim Hanyoung , Mohanty Aruna Kumar , Yang Jiyeon , Piao Longhai , Joo Sang‐Woo , Han Joong Tark , Han Jong Hun , Paik Hyun‐jong
Published: July 2021

Silver nanowires (AgNWs) with low sheet resistances are excellent potential candidates for high‐performance wearable electrothermal heaters operated through Joule heating. However, the thermal oxidation and electrical instability of AgNWs caused by high contact resistance and poor adhesion to different substrates considerably limit their use in devices. Graphene is used in a AgNW/graphene hybrid owing to its low oxygen permeability, lower contact resistance with AgNWs, and good van der Waals interactions. Molecular‐level contacts between AgNWs and graphene must be achieved to maximize the synergy of these properties. In this study, a multifunctional polymer possessing styrene sulfonate‐based copolymer and disulfide groups is designed; these groups allow the simultaneous dispersion of AgNWs and graphene in an aqueous solution through self‐assembly. Since this polymer promotes molecular‐level contact between AgNWs and graphene, the oxidation and Joule‐heating stabilities of the hybrid dramatically increase. In addition, a freestanding AgNW/graphene film is readily prepared, exhibiting good attachable properties on various substrates and superior stability under harsh conditions (85 °C and 85% relative humidity for 7 days). The AgNW/graphene hybrid film displays a low sheet resistance (0.36 ± 0.02 Ω sq−1) with good performance as a high‐performance electrothermal heater (200 °C at 1.5 V).
Multiplexing Vectorial Holographic Images with Arbitrary Metaholograms
Authors: Wan Weiping , Yang Wenhong , Feng Hang , Liu Yilin , Gong Qihuang , Xiao Shumin , Li Yan
Published: July 2021

Metasurfaces achieving arbitrary phase profiles within ultrathin thickness, emerge as miniaturized, ultracompact, and kaleidoscopic nanophotonic platforms. However, it is often required to segment or interleave independent subarray metasurfaces to multiplex holograms in a single nanodevice, which in turn affects the device's compactness and channel capacity. Here, a flexible strategy is proposed for multiplexing vectorial holographic images by controlling the phase distributions of holographic images in far field. Benefitting from precisely controlling the phase difference of reconstructed images through the modified Gerchberg–Saxton algorithm, two different holographic images are independently designed for the circular light by two interleaved metasurfaces and an extra vectorial hologram is flexibly encrypted in far field without additional set of structures on the metasurface plane. An unlimited number of polarization can be achieved in the holographic image and additional information can be decrypted when different polarization‐dependent holographic images overlap. By continually varying phase difference between the incident right and left circular polarized light, the image within the overlap area can be modulated. The silicon dielectric metahologram with record absolute multiplexed efficiency (>25%) is achieved in the experiment. This technique, as far as it is known, promises an enormous data capacity as well as a high level of information security.
Further heterogeneity in Silver–Russell syndrome: PLAG1 deletion in association with a complex chromosomal rearrangement
Authors: Brereton Rebecca E. , Nickerson Sarah L. , Woodward Karen J. , Edwards Tracey , Sivamoorthy Soruba , Ramos Vasques Walters Fabiana , Chabros Vicki , Marchin Vanessa , Grumball Tanya , Kennedy Dagmara , Uzaraga Joan , Peverall Joanne , Arscott Gillian , Beilby John , Choong Catherine S. , Townshend Sharron , Azmanov Dimitar N.
Published: July 2021

Silver–Russell syndrome (SRS) is a rare genetic condition primarily characterized by growth restriction and facial dysmorphisms. While hypomethylation of H19/IGF2:IG‐DMR (imprinting control region 1 [IC1]) located at 11p15.5 and maternal uniparental disomy of chromosome 7 (upd[7]mat) are the most common genetic mechanisms responsible for SRS, the expanding body of literature describing alternative causative variants suggests SRS is a highly heterogeneous condition, also involving variation in the HMGA2‐PLAG1‐IGF2 pathway. We report a familial PLAG1 deletion in association with a complex chromosomal rearrangement. We describe two siblings with differing unbalanced chromosomal rearrangements inherited from a mother with a 5‐breakpoint balanced complex rearrangement involving chromosomes 2, 8, and 21. The overlapping but diverse phenotypes in the siblings were characterized by shared SRS‐like features, underlined by a PLAG1 whole gene deletion. Genetic analysis and interpretation was further complicated by a meiotic recombination event occurring in one of the siblings. This family adds to the limited literature available on PLAG1‐related SRS. We have reviewed all currently known cases aiming to define the associated phenotype and guide future genetic testing strategies. The heterogeneity of SRS is further expanded by the involvement of complex cytogenomic abnormalities, imposing requirements for a comprehensive approach to testing and genetic counseling.
Targeting Inflammasomes to Treat Neurological Diseases
Authors: Lünemann Jan D. , Malhotra Sunny , Shinohara Mari L. , Montalban Xavier , Comabella Manuel
Published: July 2021

Inflammasomes are multimeric protein complexes that can sense a plethora of microbe‐ and damage‐associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome‐mediated processing and secretion of proinflammatory cytokines such as interleukin (IL) 1β and IL‐18 and induction of pyroptosis, a proinflammatory form of cell death, have been associated with the development and progression of common immune‐mediated and degenerative central nervous system (CNS) diseases such as Alzheimer disease, multiple sclerosis, brain injury, stroke, epilepsy, Parkinson disease, and amyotrophic lateral sclerosis. A growing number of pharmacological compounds inhibiting inflammasome activation and signaling show therapeutic efficacy in preclinical models of the aforementioned disease conditions. Here, we illustrate regulatory mechanisms of inflammasome activation during CNS homeostasis and tissue injury. We highlight the evidence for inflammasome activation as a mechanistic underpinning in a wide range of CNS diseases and critically discuss the promise and potential limitations of therapeutic strategies that aim to inhibit the inflammasome components in neurological disorders. ANN NEUROL 2021;90:177–188
Topological Phase Transition and Topological Quantum State Transfer in Periodically Modulated Circuit‐QED Lattice
Authors: Cao Ji , Cui Wen‐Xue , Yi Xuexi , Wang Hong‐Fu
Published: July 2021

The topological properties of a circuit‐QED lattice are studied and it is found that the system undergoes a topological phase transition accompanied by the changes of Chern numbers from 2 to −1. For different lattice sizes, the energy eigenvalue spectra and the probability distributions of edge states are shown. Moreover, it is revealed that, depending on the strictly adiabatic evolution of the time‐dependent Hamiltonian, several different topological quantum state transfers between the first two sites and the last two sites can be achieved by employing the topologically protected edge states as the transfer channels. Further, it is demonstrated that, by using resonator‐based input–output process, the photonic topological edge state can be detected by measuring the average photon number in the steady state. The scheme opens up a new prospect for investigating the potential application of topological matter in quantum information processing.
Chromoselective Synthesis of Sulfonyl Chlorides and Sulfonamides with Potassium Poly(heptazine imide) Photocatalyst
Authors: Markushyna Yevheniia , Schüßlbauer Christoph M. , Ullrich Tobias , Guldi Dirk M. , Antonietti Markus , Savateev Aleksandr
Published: July 2021

Among external stimuli used to promote a chemical reaction, photocatalysis possesses a unique one—light. Photons are traceless reagents that provide an exclusive opportunity to alter chemoselectivity of the photocatalytic reaction varying the color of incident light. This strategy may be implemented by using a sensitizer capable to activate a specific reaction pathway depending on the excitation light. Herein, we use potassium poly(heptazine imide) (K‐PHI), a type of carbon nitride, to generate selectively three different products from S‐arylthioacetates simply varying the excitation light and otherwise identical conditions. Namely, arylchlorides are produced under UV/purple, sulfonyl chlorides with blue/white, and diaryldisulfides at green to red light. A combination of the negatively charged polyanion, highly positive potential of the valence band, presence of intraband states, ability to sensitize singlet oxygen, and multi‐electron transfer is shown to enable this chromoselective conversion of thioacetates.
The Mechanism of Dehydrating Bimodules in trans‐Acyltransferase Polyketide Biosynthesis: A Showcase Study on Hepatoprotective Hangtaimycin
Authors: Luo Minghe , Xu Houchao , Dong Yulu , Shen Kun , Lu Junlei , Yin Zhiyong , Qi Miaomiao , Sun Guo , Tang Lingjie , Xiang Jin , Deng Zixin , Dickschat Jeroen S. , Sun Yuhui
Published: July 2021

A bioassay‐guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis. The biosynthetic gene cluster was identified and resembles a hybrid trans‐AT PKS/NRPS biosynthetic machinery whose first PKS enzyme contains an internal dehydrating bimodule, which is usually found split in other trans‐AT PKSs. The mechanisms of such dehydrating bimodules have often been proposed, but have never been deeply investigated. Here we present in vivo mutations and in vitro enzymatic experiments that give first and detailed mechanistic insights into catalysis by dehydrating bimodules.
Cationic Carbene Analogues: Donor‐Free Phosphenium and Arsenium Ions
Authors: Olaru Marian , Mebs Stefan , Beckmann Jens
Published: July 2021

Carbenes and their analogues have constantly enthralled chemists with their intriguing reactivity of ambiphilic character stemming from their electronic structures. Phosphenium and arsenium ions are fiercely reactive cationic species, the stabilization of which has been so far achieved in the condensed phase by dispersing the positive charge through electromeric conjugation with at least one electron‐rich substituent (frequently amido groups). Although observed in the gas phase, the isolation of dicoordinate phosphenium and arsenium ions lacking such stabilizing ligands has eluded chemists for decades. Herein we show that by judicious choice of aromatic substituents, dicoordinate, donor‐free, Lewis‐superacidic phosphenium and arsenium ions can be kinetically stabilized. They feature singlet electronic ground states possessing a vacant p‐orbital and an electron lone pair with predominantly s‐character.
Consensus of fractional‐order multi‐agent systems using iterative learning control in the sense of Lebesgue‐p norm
Authors: Lan Tianyi , Li Bingqiang , Dai Mingguang
Published: July 2021

In this paper, open loop and closed loop PDα‐type fractional‐order iterative learning control algorithms with fixed topology for the fractional‐order distributed multi‐agent systems are proposed. In the sense of Lebesgue‐p norm, the convergences of the proposed methods are discussed by using the generalized Young inequality of convolution, and their convergence conditions are presented. The proposed algorithm extends the application scope of traditional iterative learning control theory. Theoretical analysis shows that by selecting the appropriate learning gain matrix, the output of each agent can completely track the desired trajectory in a limited time interval as the number of iterations increases. The feasibility and theoretical correctness of the presented algorithm are verified by numerical simulations.
Recent Advances in Light Energy Conversion with Biomimetic Vesicle Membranes
Authors: Sinambela Novitasari , Bösking Julian , Abbas Amir , Pannwitz Andrea
Published: July 2021

Lipid bilayer membranes are ubiquitous in natural chemical conversions. They enable self‐assembly and compartmentalization of reaction partners and it becomes increasingly evident that a thorough fundamental understanding of these concepts is highly desirable for chemical reactions and solar energy conversion with artificial systems. This minireview focusses on selected case studies from recent years, most of which were inspired by either membrane‐facilitated light harvesting or respective charge transfer. The main focus is on highly biomimetic liposomes with artificial chromophores, and some cases for polymer‐membranes will be made. Furthermore, we categorized these studies into energy transfer and electron transfer, with phospholipid vesicles, and polymer membranes for light‐driven reactions.
Keep your eye on…
Authors: Knopf Alison
Published: July 2021

The sequelae of parental death

Overdiagnosis of ADHD — or not?

Collaborating with pediatricians for psychosis referrals

The link between being bullied and gun violence
Sentencing juveniles to life without parole ignores science
Authors: Paccione‐Dyszlewski Margaret
Published: July 2021

In a decision on April 22, 2021 the Supreme Court of the United States ruled that the Eighth Amendment permits juvenile offenders convicted of homicide to be sentenced to life without parole as long as “the sentence is not mandatory and the sentencer therefore has discretion to impose a lesser punishment.”
Mask and vaccination guidance from AAP
Authors: Knopf Alison
Published: July 2021

In updated face mask guidance issued just as schools were getting out in June, the American Academy of Pediatrics (AAP) recommended continuing well‐fitting face masks for children and teens age 2 and older who are not yet fully vaccinated.