bluuebunny/crossref_metadata_2025 huggingface dataset:
Secondary structure of some elements of 18S rRNA suggests that strongylid and a part of rhabditid nematodes are monophyletic
Authors: Aleshin Vladimir V , Kedrova Olga S , Milyutina Irina A , Vladychenskaya Natalia S , Petrov Nikolai B
Published: July 2002

Analysis of the secondary structure of 18S rRNA molecules in nematodes revealed some new traits in the secondary structure peculiar to their hairpin 17. Some of them are characteristic of all the nematodes, whereas others are characteristic exclusively of the order Rhabditida. The loss of a nucleotide pair in the highly conservative region of hairpin 17 distinguishes 18S rRNA of the Strongylida and some species of the Rhabditida from other nematodes and, moreover, from all other organisms. Hence, it is possible to regard the Strongylida and a part of the Rhabditida includingCaenorhabditis elegansas a new monophyletic taxon.
Developmentally and wound‐regulated expression of the gene encoding a cell wall copper amine oxidase in chickpea seedlings1
Authors: Rea Giuseppina , Laurenzi Maria , Tranquilli Emanuela , D'Ovidio Renato , Federico Rodolfo , Angelini Riccardo
Published: July 2002

A chickpea cDNA encoding a cell wall copper amine oxidase (CuAO) was cloned and characterised. The 2010 bp open reading frame encodes a protein of 76.5 kDa which shares significant primary structure homology with other known CuAOs. Southern blot analysis indicates that in chickpea CuAO is encoded by a single gene or a small gene family. This cDNA was essential for studying the role of CuAO during seedling development and wound healing in chickpea seedlings. CuAO transcript level and activity were modulated during seedling development in parallel with cell maturation. Moreover, mechanical wounding induced a rapid increase of CuAO mRNA accumulation and enzyme activity which remained high during the wound‐healing process. Aminoguanidine, a specific CuAO inhibitor, decreased the deposition of lignin‐suberin barrier along the lesion. CuAO may be a limiting factor in H2O2 production in the cell wall of chickpea seedlings and its expression seems to integrate with the remodelling of plant cell wall occurring during ontogenesis and wound healing.
Human thymidine kinase 2: molecular cloning and characterisation of the enzyme activity with antiviral and cytostatic nucleoside substrates
Authors: Wang Liya , Munch-Petersen Birgitte , Herrström Sjöberg Anita , Hellman Ulf , Bergman Tomas , Jörnvall Hans , Eriksson Staffan
Published: July 2002

Based on amino acid sequence information from purified mitochondrial thymidine kinase (TK2), a cDNA of 1930 bp was cloned, containing an open reading frame encoding 232 amino acid residues starting with the N‐terminal sequence determined from the native human protein preparation. Northern blot analysis with the cDNA coding region demonstrated several TK2 mRNAs, with 2 and 4 kb forms present in many tissues. We also characterised N‐terminally truncated (starting at position 18) human TK2 with pharmacologically important antiviral and cytostatic nucleoside analogues. Results were highly similar to those with the native TK2 preparation. The anti‐leukaemic drug arabinosyl cytosine is phosphorylated. The antitumour drug difluorodeoxycytidine and its metabolite difluorodeoxyuridine are good substrates, with K
m values of 66 and 29 μM, respectively, and a relative V
max of 0.6 compared to that of thymidine. Negative cooperativity was found with thymidine and the anti‐HIV drug 3′‐azidothymidine, but the reaction followed Michaelis‐Menten kinetics with deoxycytidine, arabinosyl cytosine, and arabinosyl thymine. The results demonstrate a broad substrate specificity and complex kinetics, and suggest a role for TK2 in the activation of chemotherapeutic nucleoside analogues.
An alternative oxidase monoclonal antibody recognises a highly conserved sequence among alternative oxidase subunits
Authors: Finnegan Patrick M. , Wooding Anthea R. , Day David A.
Published: July 2002

The alternative oxidase is found in the inner mitochondrial membranes of plants and some fungi and protists. A monoclonal antibody raised against the alternative oxidase from the aroid lily Sauromatum guttatum has been used extensively to detect the enzyme in these organisms. Using an immunoblotting strategy, the antibody binding site has been localised to the sequence RADEAHHRDVNH within the soybean alternative oxidase 2 protein. Examination of sequence variants showed that A2 and residues C‐terminal to H7 are required for recognition by the monoclonal antibody raised against the alternative oxidase. The recognition sequence is highly conserved among all alternative oxidase proteins and is absolutely conserved in 12 of 14 higher plant sequences, suggesting that this antibody will continue to be extremely useful in studying the expression and synthesis of the alternative oxidase.
Cloning and characterization of hGMEB1, a novel glucocorticoid modulatory element binding protein
Authors: Thériault Jimmy R , Charette Steve J , Lambert Herman , Landry Jacques
Published: July 2002

A 21‐bp element called glucocorticoid modulatory element (GME) modulates the glucocorticoid receptor‐mediated responses via the binding of an as yet poorly characterizedtrans‐acting complex of proteins containing the 88‐kDa GMEB1 and the 67‐kDa GMEB2. Using heat shock protein 27 (HSP27) as bait in the yeast two‐hybrid assay, we cloned a 1.83‐kb cDNA encoding a novel 573‐amino acid protein called human GMEB1 (hGMEB1). hGMEB1 possesses a KDWK domain, contains sequences almost identical (36/38) to three tryptic peptides of rat GMEB1 and shares 38% identity with rat GMEB2. hGMEB1 is ubiquitously expressed as a 85‐kDa protein in all cell lines and tissues examined. In vitro translated hGMEB1 bound specifically to GME oligonucleotides yielding a complex of similar size to the complex obtained using rat liver nuclear extracts. Both complexes were supershifted with an antibody specific to hGMEB1. Co‐immunoprecipitation experiments confirmed the in vivo interaction of HSP27 with hGMEB1.
CuI‐semiquinone radical species in plant copper‐amine oxidases
Authors: Medda Rosaria , Padiglia Alessandra , Bellelli Andrea , Pedersen Jens Z. , Finazzi Agrò Alessandro , Floris Giovanni
Published: July 2002

The intermediate CuI‐semiquinone radical species in the catalytic mechanism of copper‐amine oxidase from Lens esculenta and Pisum sativum seedlings has been studied by optical, Raman resonance and ESR spectroscopies and by stopped‐flow and temperature‐jump measurements. Treatment of highly purified enzyme preparations with good, poor or suicide substrates, under anaerobic and aerobic conditions, at different pH values and temperatures, makes it possible to generate, detect and characterize this free radical intermediate.
Reduction of G‐box binding factor DNA binding activity, but not G‐box binding factor abundance, causes the downregulation of RBCS2 expression during early tomato fruit development
Authors: Baum Katja , Wienand Udo , Meier Iris
Published: July 2002

The downregulation of RBCS2 promoter activity during tomato fruit development has been investigated by transient gene expression. A major drop in promoter activity occurs between 5 and 25 mm fruit diameter, corresponding to the late cell division to early cell enlargement phase. This drop is abolished by a mutation of the single G‐box element necessary for high RBCS2 promoter activity in young tomato fruit. The G‐box binding activity of fruit nuclear and total protein extracts drops concomitantly with the reduction of RBCS2 promoter activity while G‐box binding factor expression is not affected. The data indicate that the developmental signal that downregulates the RBCS2 promoter acts on the regulation of DNA binding activity of constitutively expressed G‐box binding factors.
N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D lacks the ability to transphosphatidylate
Authors: Petersen Gitte , Hansen Harald S
Published: July 2002

The N‐acylphosphatidylethanolamine‐hydrolysing phospholipase D (NAPE‐PLD) generates N‐acylethanolamines, including N‐arachidonoyl‐ethanolamine (anandamide), that may be neuroprotective and analgesic. The properties of NAPE‐PLD from rat heart and brain microsomes are investigated and compared to those of other PLDs. NAPE‐PLD is inhibited by the fatty acid aminohydrolase inhibitor MAFP in high concentrations (≥100 μM) while PMSF in high concentrations (10 mM) tends to stabilise NAPE‐PLD activity. Oleate inhibits NAPE‐PLD but the enzyme is not affected by PIP2, α‐synuclein or mastoparan. Furthermore, it is for the first time reported that NAPE‐PLD is not capable of catalysing a transphosphatidylation reaction like most other known PLDs.
Role of histone acetylation and DNA methylation in the maintenance of the imprinted expression of the H19 and Igf2 genes
Authors: Pedone Paolo V. , Pikaart Michael J. , Cerrato Flavia , Vernucci Maria , Ungaro Paola , Bruni Carmelo B. , Riccio Andrea
Published: July 2002

H19 and Igf2 are linked and reciprocally imprinted genes. We demonstrate that the histones associated with the paternally inherited and unexpressed H19 allele are less acetylated than those associated with the maternal expressed allele. Cell growth in the presence of inhibitors of either histone deacetylase or DNA methylation activated the silent Igf2 allele, whereas derepression of the silent HI9 allele required combined inhibition of DNA methylation and histone deacetylation. Our results indicate that histone acetylation as well as DNA methylation contribute to the somatic maintenance of H19 and Igf2 imprinting and that silencing of the imprinted alleles of these two genes is maintained via distinct mechanisms.
Inhibition of the vacuolating and anion channel activities of the VacA toxin of Helicobacter pylori
Authors: Tombola Francesco , Oregna Federica , Brutsche Sandra , Szabò Ildikò , Del Giudice Giuseppe , Rappuoli Rino , Montecucco Cesare , Papini Emanuele , Zoratti Mario
Published: July 2002

VacA, the vacuolating cytotoxin secreted by Helicobacter pylori, is believed to be a major causative factor in the development of gastroduodenal ulcers. This toxin causes vacuolation of cultured cells and it has recently been found to form anion‐selective channels upon insertion into planar bilayers as well as in the plasmamembrane of HeLa cells. Here, we identify a series of inhibitors of VacA channels and we compare their effectiveness as channel blockers and as inhibitors of VacA‐induced vacuolation, confirming that the two phenomena are linked. This characterization opens the way to studies in other experimental systems and to the search for a specific inhibitor of VacA action.
The effect of women's role on health: the paradox
Authors: Kabira W.M. , Gachukia E.W. , Matiangi F.O.
Published: July 2002

Most societies in Africa are patriarchal in nature. Traditional Africa has allocated the role of nurturing, and ensuring the health of the family and the community as a whole to women. From the age of six, girls begin to work with their mothers, cleaning, sweeping, nursing and caring for the younger children, the aged and the sick. Therefore, the female child is customarily socialized as the custodian of family health. Because women are traditionally responsible for health in African countries and their status in society is low, the status of the health sector has received less attention than other sectors. The paradox of entrusting the woman with the responsibility of health and at the same time denying her the opportunities to influence policies remains a major obstacle. Factors that influence women's health in Africa most commonly include poverty, poor education and poor nutrition. Access to education for African women is a major problem. The impact of a poorly educated mother is passed on to the daughter. In some parts of Africa, female circumcision contributes to the high school dropout rates. Once the girls are withdrawn from school to participate in the ceremonies, they do not return to school. They are encouraged and socialized towards marriage. Africa has the highest fertility rate, the lowest life expectancy (49 years for males and 52 for females, the highest infant mortality rate (114 deaths per 1000 live births); the highest maternal mortality rate and the highest dependency ratio (47% under 15 years and only 3% over 65). The foregoing factors call for urgent attention to health issues, especially those which affect women who are the traditional health providers. There is an unacceptably high rate of unsafe abortion which accounts for up to 30% of maternal mortality in some African countries, and there is growing concern over teenage pregnancies in some African countries. Nearly two‐thirds of the cases of septic abortions are in the 15–19‐year age group and yet African governments and the legal systems would rather not deal with abortion. The gap between mortality and fertility is widening; it doubled between 1972 and 1994 and is expected to double in 2017. In many African countries, children are the only ‘goods’ that women are expected to produce. Unless this attitude changes, fertility rates will continue to rise as women continue to search for their place in society and justify their place within marriages and relationships through child bearing.
Modulation of glutamate neurotoxicity on mesencephalic dopaminergic neurons in primary cultures by the presence of striatal target cells
Authors: Mateu Guylaine , Privat Alain , Thibault Jean , Vignon Jacques
Published: July 2002

Glutamate toxicity was compared in substantia nigra (SN)/striatum (STR) and SN/cerebellum (CRB) co‐cultures on both the entire neuronal population (neuron specific enolase (NSE) immunopositive cells) and dopaminergic neurons (tyrosine hydroxylase (TH) immunopositive cells). In SN/CRB co‐cultures NSE‐ and TH‐positive cells were more sensitive to glutamate‐induced toxicity than in SN/STR co‐cultures. Moreover, in SN/STR co‐cultures as compared to SN/CRB and SN cultures, glutamate toxicity was prevented to a larger extent by TCP, a non‐competitive NMDA antagonist. These results suggest that target cells induce a differential expression of the different glutamate receptor subtypes in mesencephalic dopaminergic cells. Alternatively, the presence of target cells may induce the selective development of a subpopulation of dopaminergic neurons expressing predominantly NMDA receptors.
A double-blind comparison of sertraline and clomipramine in outpatients with obsessive-compulsive disorder
Authors: Bisserbe JC , Lane RM , Flament MF ,   France-Belgian OCD Study Group
Published: July 2002

The aim of this study was to compare the efficacy, safety, and tolerability of sertraline and clomipramine in the treatment of obsessive-compulsive disorder (OCD). Outpatients with DSM-III-R defined OCD for 1 year or longer and scores of ≥ 20 on the YaleBrown Obsessive Compulsive Scale (Y-BOCS), ≥ 7 on the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH-OC), ≥ 4 on the Clinical Global Impression Severity of Illness Scale (CGI-S) and ≤17 on the Hamilton Depression Scale (17 item HAMD) were randomized to sertraline (n= 86) or clomipramine (n= 82) once daily for 16 weeks. Initial daily doses of sertraline and clomipramine were 50 mg. After a minimum of 4 weeks, these doses could be increased by 50 mg increments every 2 weeks to a maximum of 200 mg daily if the response was thought inadequate. Efficacy was assessed at the end of 1, 2, 4, 6, 8, 12 and 16 weeks of therapy using the Y-BOCS, NIMH-OC, CGI-S, CGI Improvement Scale (CGI-I) and Clinical Anxiety Scale (CAS). One hundred sixty-eight patients were randomized and received at least one dose of double-blind medication; 86 received sertraline and 82 clomipramine. Mean final daily doses at final visit were clomipramine 90 mg (efficacy evaluable patients 101 mg, completers 110 mg), and sertraline 129 mg (efficacy evaluable patients 132 mg, completers 136 mg). Mean baseline Y-BOCS, NIMH-OC and CGI-S totals were 27.7, 10.1 and 5.5, respectively, for sertraline and 27.4, 9.9 and 5.5, respectively, for clomipramine. Sertraline demonstrated greater efficacy than clomipramine in the intent-to-treat patient group: mean baseline to final visit changes were 50.8% (Y-BOCS), 41.9% (NIMH-OC) and 37.7% (CGI-S) for sertraline and 42.9% (Y-BOCS), 33.8% (NIMH-OC) and 30.0% (CGI-S) for clomipramine (P< 0.05). The number of patients withdrawing because of adverse events was substantially greater for clomipramine (26%) than sertraline (11%) (P< 0.05). The most frequent adverse events for clomipramine were dry mouth (20%), anxiety (17%), constipation (16%), nausea (15%) and somnolence (11%), and for sertraline, diarrhea (12%) and nausea (12%). In this study, sertraline was more effective than clomipramine in the intent-to-treat analysis. The difference in efficacy between the treatments is almost wholly accounted for by a greater number of clomipramine withdrawals due to the poor patient acceptance of clomipramine. The superior tolerability of sertraline and the lower rate of premature treatment withdrawal relative to clomipramine may offer considerable quality of life and compliance benefits in the long-term management of a chronic disorder such as OCD.
The efficacy of a psychiatric halfway house: a study of hospital recidivism and global outcome measure
Authors: Vaslamatzis G , Katsouyanni K , Markidis M
Published: July 2002

The authors investigated the post-halfway house outcome of a sample of 41 former residents of the halfway house of the Department of Psychiatry, Athens University. Two criteria were used: hospital recidivism and global ratings of outcome (which was assessed on the basis of three parameters: rehospitalization, employment and independent living). Mean duration from the time of departure was 32 months (range: 8–52 months). Within this period good outcome and non-recidivism were related with compliance to pharmacotherapy. Most recidivists also had a shorter stay in the halfway house and cases with successful outcome tended to be evaluated higher on the “Behaviour in Halfway House Scale” at the end of the residency.
Effect of tandospirone on tardive dyskinesia and parkinsonian symptoms
Authors: Yoshida K , Sugita T , Higuchi H , Hishikawa Y
Published: July 2002

The authors examined the effect of tandospirone on tardive dyskinesia (TD) and parkinsonian symptoms in an open study. Tandospirone did not bring about any favourable effect on TD, but it had a good effect on the parkinsonian symptoms.
Enzymatic activity of the blue light‐regulated phosphodiesterase BlrP1 from Klebsiella pneumoniae shows a nonlinear dependence on light intensity
Authors: Shibata Kosei , Nakasone Yusuke , Terazima Masahide
Published: March 2021

The blue light‐regulated phosphodiesterase BlrP1 from Klebsiella pneumoniae hydrolyzes cyclic dimeric guanosine monophosphate (GMP) in a blue light‐dependent manner. It contains a photosensing BLUF domain and a functional EAL domain. Previously, it was reported that conformational changes in the dimer upon light illumination occurred only when both protomers of the dimer were excited. Based on this observation, it was proposed that BlrP1 might be a nonlinear light intensity sensor. To test this, here, the correlation between the turnover number of the hydrolysis reaction (kcat) and the fraction of the excited protein (fred) was measured by simultaneously monitoring the reaction rate and fred. Our results show that kcat is proportional to fred2. Thus, BlrP1 works as a nonlinear light intensity sensor to sense a strong light environment.
Telomerase reverse transcriptase activates transcription ofmiR500Ato inhibit Hedgehog signalling and promote cell invasiveness
Authors: Bernabé‐García Manuel , Martínez‐Balsalobre Elena , García‐Moreno Diana , García‐Castillo Jesús , Revilla‐Nuin Beatriz , Blanco‐Alcaina Elena , Mulero Victoriano , Alcaraz‐Pérez Francisca , Cayuela María L.
Published: March 2021

Telomerase reverse transcriptase (TERT) maintains telomere homeostasis, thus ensuring chromosome stability and cell proliferation. In addition, several telomere‐independent functions of human TERT have been described. In this study, we report that TERT binds directly to the TCF binding elements located upstream of the oncomiR miR500A, and induces its transcription. This function was independent of the telomerase activity, as shown with experiments using catalytically inactive TERT and inhibitors of TERT and the TERT RNA component. miR500A was in turn found to target three key components of the Hedgehog signalling pathway: Patched 1; Gli family zinc finger 3; and Cullin 3, thereby promoting cell invasion. Our results point to the crucial role of the TERT–miR500A–Hedgehog axis in tumour aggressiveness and highlight the therapeutic potential of targeting noncanonical TERT functions in cancer.
Interleukin‐36α suppresses growth of non‐small cell lung cancer in vitro by reducing angiogenesis
Authors: Xie Xiaoxiao , Hu Haoyue , He Jun , Liu Yanyang , Guo Fengzhu , Luo Feng , Jiang Ming , Wang Li
Published: March 2021

Interleukin (IL)‐36α, a newly recognized IL‐1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL‐36α has potential anticancer effects against certain types of cancer. However, the expression pattern and functional role of IL‐36α in non‐small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL‐36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL‐36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion and shorter overall survival (OS). Intratumoral IL‐36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in patients with NSCLC. Overexpression of IL‐36α in lung cancer cells did not disturb cell proliferation, apoptosis or cell‐cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL‐36α reduced the expression and secretion of vascular endothelial growth factor A through inhibiting hypoxia‐inducible factor 1α expression. Finally, decreased IL‐36α expression was associated with high microvessel density and vascular endothelial growth factor A in patients with NSCLC. Together, our findings suggest that IL‐36α expression is a valuable marker indicating poor prognosis in patients with NSCLC.
The continued influence effect: Examining how age, retraction, and delay impact inferential reasoning
Authors: Miller Alyssa L. , Wissman Kathryn T. , Peterson Daniel J.
Published: March 2021

Research suggests exposure to misinformation continues to impact belief and reasoning, even if that misinformation has been corrected (referred to as the Continued Influence Effect, CIE). The proposed experiment explores two potentially important factors that may impact the effect: (a) learner age and (b) length of delay between retraction and final test. During initial learning, participants (both young and older adults) will read six scenarios in which a critical piece of misinformation is either retracted or not retracted. Following no delay, a short (10 min) delay, or a long (2 days) delay, participants will then answer inferential reasoning questions about the previously‐studied scenarios to evaluate how (if at all) the prior retraction impacts reliance on misinformation. Outcomes will better help us to understand the ways in which misinformation (even following retraction) impacts reasoning, an issue of exceeding importance as the proliferation of fake news shows no signs of slowing.
Actuator fault estimation based on generalized learning observer for quasi‐linear parameter varying systems
Authors: Zetina‐Rios Israel I. , Osorio‐Gordillo Gloria‐L. , Vargas‐Méndez Rodolfo A. , Madrigal‐Espinosa Guadalupe , Astorga‐Zaragoza Carlos‐M.
Published: March 2021

This article presents a generalized learning observer (GLO) design for the simultaneous estimation of states and actuator faults for polytopic quasi‐linear parameter varying systems. The proposed approach is based on the use of a GLO, which generalized the existing results on the proportional‐integral observers. Conditions of existence and stability of the observer are given through the stability analysis in the sense of Lyapunov. Its design is obtained in terms of a set of linear matrix inequalities. The performance of the proposed method is evaluated by simulation in a one‐link‐flexible joint robot system.
Study: NSDUH poor judge of heroin use
Authors: Knopf Alison
Published: March 2021

The National Survey on Drug Use and Health (NSDUH), released annually by the Substance Abuse and Mental Health Services Administration, is a poor way to estimate heroin use, a study published online March 2 in Addiction has found. Researchers, policymakers, lawmakers and reporters have relied on this survey for decades, not only in the United States but across the world. And in fact, it's likely one of the best general population surveys (GPSs) on drug use, the research found. But as it turns out, that's not saying much when it comes to a rare and highly stigmatized behavior like heroin use.
Study shows why much of OUD treatment falls short of optimal duration
Authors: Enos Gary
Published: March 2021

Newly published research has shed further light on the factors that influence retention in medication treatment for opioid use disorder (OUD), confirming that variables such as young age and referral from the justice system increase the likelihood of treatment discontinuation before six months. Results of the study also suggest that many outpatient treatment programs are ignoring the evidence base for extended treatment and are using medications such as buprenorphine as a short‐term taper strategy only.
DuPage County sheriff allows methadone after lawsuit
Authors: Knopf Alison
Published: March 2021

Before the lawsuit filed by the Legal Action Center and colleagues demanding that the DuPage County sheriff and jail allow Christine Finnigan to get her methadone throughout her 30‐day stay in jail for a 2016 DWI conviction (before she was in treatment), things looked grim (see “Jail may force methadone patient to detox when she goes in next week,” ADAW Feb. 15, https://onlinelibrary.wiley.com/doi/10.1002/adaw.32969). But days before Finnigan was due to report to jail, the sheriff changed course. “It feels great to tell you that this morning, the DuPage County Jail reported to the court that it will permit Chris Finnigan to get her methadone throughout her stay at the jail,” the Legal Action Center's Sally Friedman told ADAW Feb. 26.
Resistance to SUD licensure: California hypocrisy
Authors: Prichard Michael
Published: March 2021

California is famous for its beautiful coastlines, majestic mountains, vast deserts and lush agricultural regions that grow much of the world's produce. California is also known for its technological innovations and progressive attitudes in its pursuit of social equality. I believe the positive aspects of the Golden State overshadow many of the negative realities and significant social inequalities that have existed here for decades. Social inequality is particularly glaring related to people who have substance use disorder (SUD).
Polydiketopyrrolopyrroles Carrying Ethylene Glycol Substituents as Efficient Mixed Ion‐Electron Conductors for Biocompatible Organic Electrochemical Transistors
Authors: Krauss Gert , Meichsner Florian , Hochgesang Adrian , Mohanraj John , Salehi Sahar , Schmode Philip , Thelakkat Mukundan
Published: March 2021

A comprehensive investigation of four polydiketopyrrolopyrroles (PDPPs) with increasing ethylene glycol (EG) content and varying nature of comonomer is presented, and guidelines for the design of efficient mixed ion‐electron conductors (MIECs) are deduced. The studies in NaCl electrolyte‐gated organic electrochemical transistors (OECTs) reveal that a high amount of EG on the DPP moiety is essential for MIEC. The PDPP containing 52 wt% EG exhibits a high volumetric capacitance of 338 F cm−3 (at 0.8 V), a high hole mobility in aqueous medium (0.13 cm2 V−1 s−1), and a μC* product of 45 F cm−1 V−1 s−1. OECTs using this polymer retain 97% of the initial drain‐current after 1200 cycles (90 min of continuous operation). In a cell growth medium, the OECT‐performance is fully maintained as in the NaCl electrolyte. In vitro cytotoxicity and cell viability assays reveal the excellent cell compatibility of these novel systems, showing no toxicity after 24 h of culture. Due to the excellent OECT performance with a considerable cycling stability for 1200 cycles and an outstanding cell compatibility, these PDPPs render themselves viable for in vitro and in vivo bioelectronics.
Ductile‐Metal Ag as Buffer Layer for Flexible Self‐Powered Ag2S Photodetectors
Authors: Lei Yan , Gu Longyan , Yang Xiaogang , Lin Yuan , Zheng Zhi
Published: March 2021

The rigid nature of inorganic semiconductors makes them rarely use in flexible devices till now. For the first time, ductile‐metal Ag is used as buffering layer to bond the inorganic semiconductor thin films and polymer substrate forming a sandwich structure, which has outstanding flexible photoelectric character. The ductile thin Ag layer under Ag2S thin film acts as electrode and buffering material between the Ag2S and polyimide (PI) layers. The strong bonding interaction between Ag2S and Ag can reduce the stress force in Ag2S thin films that is generated during bending, which enhances its flexibility. The resulted Ag2S/Ag/PI film shows excellent electrical performance retentivity. After more than 104 cycles bending test, the conductivity of the Ag2S/Ag/PI films has almost not changed. The prepared Au/PEDOT:PSS/Ag2S/Ag/PI photodetectors are stable in air or N2. It can bear a small bending radius as low as 1.5 mm for ≈4000 bending cycles test without drastic performance decay. In addition, the Ag2S/Ag based flexible photodetectors show a wide spectral response from ultraviolet to near infrared.
Palladium‐Catalyzed Regioselective C−H Arylation of 4‐Azaindazole at C3, C5 and C7 Positions
Authors: Faarasse Soukaina , El Kazzouli Saïd , Bourzikat Otmane , Bourg Stéphane , Aci‐Sèche Samia , Bonnet Pascal , Suzenet Franck , Guillaumet Gérald
Published: March 2021

Direct and site‐selective C5 and C7 palladium‐catalyzed C−H arylations of 4‐azaindazole N‐oxide have been achieved. A bidentate ligand and Pd(OAc)2 catalyst in toluene promoted the activation of C5 position, while a phosphine ligand and PdCl2 catalyst in DMA directed the arylation at C7 position. Using this new method, the synthesis of C5, C7‐diarylated 4‐azaindazole N‐oxides as well as the C3, C5, C7‐triarylated 4‐azaindazoles was achieved towards future medicinal compounds development.

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Practical Stereoselective Synthesis of C3‐Spirooxindole‐ and C2‐Spiropseudoindoxyl‐Pyrrolidines via Organocatalyzed Pictet‐Spengler Reaction/Oxidative Rearrangement Sequence
Authors: Kondo Masaru , Matsuyama Naoki , Aye Tin Z. , Mattan Irshad , Sato Tomoyuki , Makita Yoshinori , Ishibashi Masami , Arai Midori A. , Takizawa Shinobu , Sasai Hiroaki
Published: March 2021

A stereoselective synthetic route to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines was accomplished by an enantioselective organocatalyzed Pictet‐Spengler reaction of tryptamines and isotryptamines followed by a diastereoselective oxidative rearrangement using eco‐friendly oxidants (i. e., NaOCl ⋅ 5H2O and Oxone®). This sequential reaction enables rapid access to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines in a one‐pot process. A Wnt signaling inhibitory assay of the prepared enantioenriched spiro compounds demonstrated that they exhibited moderate activities.

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Small Molecule Imaging Agent for Mutant KRAS G12C
Authors: Koch Peter D. , Quintana Jeremy , Ahmed Maaz S. , Kohler Rainer H. , Weissleder Ralph
Published: March 2021

Multiple potent covalent inhibitors for mutant KRAS G12C have been described and some are in clinical trials. These small molecule inhibitors potentially allow for companion imaging probe development, thereby expanding the chemical biology toolkit to investigate mutant KRAS biology. Herein, a series of fluorescent companion imaging drugs for KRAS G12C, using two scaffolds, ARS‐1323 and AMG‐510 is synthesized and tested. Four fluorescent derivatives of each by attaching BODIPY dyes are created. It is found that two fluorescent derivatives (BODIPY FL and BODIPY TMR) of ARS‐1323 bind mutant KRAS and can be used for biochemical binding screens. Unfortunately, these drugs cannot be used as direct imaging agents in cells, likely because of nonspecific membrane labeling. To circumvent this challenge, a two step procedure is then used in cancer cells where an ARS‐1323 alkyne is used for target binding followed by fluorescence imaging after in situ click chemistry with picolyl azide Alexa Fluor 647. It is shown that this approach can be used to image mutant KRAS G12C directly in cells. Given the current lack of mutant KRAS G12C specific antibodies, these reagents can be useful for specific fluorescence imaging.
Impact of preoperative muscle quality on postoperative severe complications after radical gastrectomy for gastric cancer patients
Authors: Matsui Ryota , Inaki Noriyuki , Tsuji Toshikatsu
Published: March 2021

Background

Preoperative sarcopenia is an important risk factor for postoperative complications in patients with gastric cancer. However, the relationship between muscle quality and postoperative complications in patients with gastric cancer is inadequately studied. Therefore, we investigated the impact of preoperative muscle quality on severe postoperative complications after radical gastrectomy.

Methods

A total of 840 patients who underwent radical gastrectomy for p‐stages I–III primary gastric cancer between April 2008 and June 2018 with preoperative computed tomography (CT) scans and body composition analysis were included. We measured intramuscular adipose tissue content (IMAC) as an indicator of muscle quality. A higher IMAC signified a poorer quality. All statistical analyses were performed with EZR, and a P‐value < 0.05 was considered statistically significant.

Results

The low‐IMAC and high‐IMAC groups had 422 (50.2%) and 418 (49.8%) patients, respectively. The latter were older (P < 0.001), had higher body mass index (BMI) (P < 0.001), and higher rates of chronic kidney disease (CKD) (P = 0.002) and diabetes (P < 0.001). They had lower skeletal muscle indexes (SMI) (P = 0.011) and higher visceral fat areas (VFA) (P < 0.001). They also experienced more intraoperative blood loss (P < 0.001) and greater complications (P = 0.016). Multivariate analysis showed that high‐IMAC was an independent risk factor for severe complications (odds ratio: 2.260, 95% confidence interval: 1.220‐4.190, P = 0.010).

Conclusions

Poor preoperative muscle quality is an independent risk factor for severe postoperative complications after radical gastrectomy in patients with gastric cancer.
A novel homozygous RIPK4 variant in a family with severe Bartsocas‐Papas syndrome
Authors: Dinçer Tuba , Gümüş Evren , Toraman Bayram , Er İdris , Yildiz Gokhan , Yüksel Zafer , Kalay Ersan
Published: March 2021

Bartsocas‐Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor‐interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon‐intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell‐based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family.
Carbene‐Catalyzed N,N‐Nucleophilic Activation of Thioureas for Access to Pyrimidinthione Derivatives
Authors: Cao Liya , Li Tingting , Chi Yonggui Robin , Jin Zhichao
Published: March 2021

An N‐heterocyclic carbene‐catalyzed [3+3] cycloaddition reaction of acylthioureas with ynals is reported. Both N atoms in the thiourea substrate are activated as nucleophiles and incorporated inside the ring system of the product. Pyrimidinthione derivatives bearing various substituents and substitution patterns are afforded as the products in moderate to good yields.
A Heat‐Activated Drug‐Delivery Platform Based on Phosphatidyl‐(oligo)‐glycerol Nanocarrier for Effective Cancer Treatment
Authors: Hossann Martin , Hirschberger Johannes , Schmidt Rebecca , Baumgartner Christine , Zimmermann Katja , Baer Silke , Ratzlaff Christina , Peller Michael , Troedson Karin , Limmer Simone , Brühschwein Andreas , Dörfelt Rene , Kreutzmann Nina , Wess Gerhard , Knösel Thomas , Schagon Olaf , Fischer Johannes , Grüll Holger , Willerding Linus , Schmidt Michael , Meyer-Lindenberg Andrea , Issels Rolf D. , Schwaiger Markus , Eggermont Alexander M. , ten Hagen Timo L. , Lindner Lars H.
Published: March 2021

The potential of cancer drugs is not fully exploited due to low tumor uptake and occurrence of systemic side effects, limiting maximum tolerated dose. Actively targeted nanocarriers improve efficacy while minimizing off‐target toxicity. Herein, it is the first time a drug‐delivery platform for heat‐triggered intravascular drug release is described, based on synthetic phosphatidyl‐(oligo)‐glycerols from organic synthesis to preclinical investigation in feline patients. For the nanocarrier formulated doxorubicin (DOX), superior tumor drug delivery and antitumor activity compared with free DOX, conventional liposomal DOX (Caelyx), and temperature‐sensitive lysolipid‐containing DOX‐liposomes in rat sarcoma are demonstrated. In a comparative oncological study with neoadjuvant treatment of feline sarcoma, a metabolic response determined with 18 F‐FDG‐positron emission tomography/magnetic resonance imaging (PET/MRI) and histopathological response after tumor resection are significantly better compared with free DOX, potentially by overcoming drug resistance based on improved intratumoral drug distribution. This novel drug‐delivery platform has great potential for the treatment of locally advanced tumors in humans.
Development of Hydrogel‐Based Sprayable Wound Dressings for Second‐ and Third‐Degree Burns
Authors: He Jacqueline Jialu , McCarthy Colleen , Camci-Unal Gulden
Published: March 2021

On‐site, prehospital care is vital for minimizing the severity of injuries caused by acute burns, especially those of the second and third degrees. Burn wounds typically have irregular shapes and depths and cover a large total body area. Due to the severity and complexity of burn wounds, traditional sheet‐like wound dressings are not always suitable. Alternatively, sprayable wound dressings can be used for convenient, quick, and large‐scale dressing changes. They can also prevent infection and secondary trauma depending on their reagent content. Sprayable wound dressings function as a therapeutic barrier that provides moisturization and pain relief, absorbs extrudates, protects against bacterial infections, and acts as a delivery system for small molecules and drugs. This review discusses the recent developments in sprayable hydrogel‐based wound dressings for high‐degree burns. An introduction to burn wound classifications, the ideal burn dressing designs and characteristics, and the current availability of commercial spray‐on burn dressings are presented. To achieve the optimal healing capacities using sprayable wound dressings, researchers are currently focusing on modifying the solution viscosities, propellant systems, and pump nozzle designs for spray formulations. Finally, the use of hydrogel‐based dressings to replace skin graft surgeries for tissue regeneration is discussed.
Segmentierte Flow‐Prozesse zur Überwindung von Limitierungen der Ganzzell‐Biokatalyse in Gegenwart von organischen Lösungsmitteln
Authors: Adebar Niklas , Nastke Alina , Löwe Jana , Gröger Harald
Published: March 2021

In der modernen Prozessentwicklung spielt Biokatalyse eine immer gewichtigere Rolle, wobei die Benutzung von Ganzzellkatalysatoren häufig eine bevorzugte Form dieser Biokatalysatoren darstellt. Die Anwendung von Ganzzellkatalysatoren in organischen zweiphasigen Batch‐Synthesen ist jedoch oft durch Einschränkungen im Hinblick auf Stofftransfer, Emulsionsbildung, aufwändiger Aufarbeitung und damit verbundenen geringen Ausbeuten beeinträchtigt. In diesem Beitrag zeigen wir, dass unter Zuhilfenahme von segmentierten Flow‐Prozessen eine effiziente Ganzzellkatalyse in zweiphasigen Medien ermöglicht wird. Die Leistungsfähigkeit solcher segmentierter Flow‐Prozesse ist dabei exemplarisch an drei unterschiedlichen Biotransformationen dargestellt. Zum Beispiel wurde in einem solchen Flow‐Prozess eine 3‐fache Steigerung des Umsatzes von 34 % auf >99 % verbunden mit einer erheblich vereinfachten Aufarbeitung erzielt, die zu einer 1.5‐fachen Steigerung der Ausbeute von 44 % auf 65 % im Vergleich zum analogen Batch‐Prozess führte.
An Aromatic Micelle‐Based Saccharide Cluster with Changeable Fluorescent Color and its Protein Interactions
Authors: Narita Haruna , Catti Lorenzo , Yoshizawa Michito
Published: March 2021

To develop a new type of synthetic saccharide clusters with changeable fluorescent colors, we herein designed a multisaccharide‐coated aromatic micelle. The new cluster forms in water through the quantitative assembly of bent polyaromatic amphiphiles bearing three mannose groups. The spherical assembly, with a 2 nm‐sized polyaromatic core and ca. 18 saccharide pendants, is stable even under high dilution conditions (up to 0.02 mM). The emission intensity and color of the saccharide cluster can be altered from moderate blue (ΦF=19 %) to strong red, orange, and green (ΦF up to 67 %) upon encapsulation of hydrophobic fluorescent dyes in water. Moreover, the present fluorescent clusters, both with and without the dyes, display selective interactions with mannose‐binding proteins in vitro.
Ferroelectric and Spin Crossover Behavior in a Cobalt(II) Compound Induced by Polar‐Ligand‐Substituent Motion
Authors: Akiyoshi Ryohei , Komatsumaru Yuki , Donoshita Masaki , Dekura Shun , Yoshida Yukihiro , Kitagawa Hiroshi , Kitagawa Yasutaka , Lindoy Leonard F. , Hayami Shinya
Published: March 2021

Ferroelectric spin crossover (SCO) behavior is demonstrated to occur in the cobalt(II) complex, [Co(FPh‐terpy)2](BPh4)2⋅3ac (1⋅3 ac; FPh‐terpy=4′‐((3‐fluorophenyl)ethynyl)‐2,2′:6′,2′′‐terpyridine) and is dependent on the degree of 180° flip–flop motion of the ligand's polar fluorophenyl ring. Single crystal X‐ray structures at several temperatures confirmed the flip–flop motion of fluorobenzene ring and also gave evidence for the SCO behavior with the latter behavior also confirmed by magnetic susceptibility measurements. The molecular motion of the fluorobenzene ring was also revealed using solid‐state 19F NMR spectroscopy. Thus the SCO behavior is accompanied by the flip–flop motion of the fluorobenzene ring, leading to destabilization of the low spin cobalt(II) state; with the magnitude of rotation able to be controlled by an electric field. This first example of spin‐state conversion being dependent on the molecular motion of a ligand‐appended fluorobenzene ring in a SCO cobalt(II) compound provides new insight for the design of a new category of molecule‐based magnetoelectric materials.
Review on synthesis of pyrrole derivatives promoted by nanoparticles
Authors: Rostami Hedieh , Shiri Lotfi
Published: March 2021

Pyrrole derivatives are a special class of heterocycle compounds that have many biological and pharmacological activities. Also, these compounds are one important portion of natural products which give particular properties to these compounds. In recent years, use of different nanoparticles for the organic synthesis is increased. In this review, we focused on the application of different nanoparticles in the synthesis of pyrrole derivatives.
Host‐guest nanosized coordination complexes based on Ag‐isonicotinic acid‐H2O and Ni‐4,4′‐bipyridine‐aminobenzic acid‐H2O as potentially active anticancer and antimicrobial agents
Authors: Badr El‐din Ahmed S. , Etaiw Safaa Eldin H. , Marie Hassan , El‐bendary Mohamed M.
Published: March 2021

Nano‐scaled coordination complexes (CC) exhibiting the structures [Ag (INH)2].OH.H2O (CC1), [Ni(4,4′‐bpy)(H2O)4](4‐aba)2.4H2O (CC2), (INH = isonicotinic acid, 4,4′‐bpy = 4,4′‐bipyridine, 4‐aba = aminobenzoate) were prepared via self‐assembly and sono‐chemical methods at ambient conditions. The structures were fully studied by single‐crystal XRD and analytical investigations. Water molecules and the hydroxyl ions act as guests connecting the discrete molecules in complex 1, whereas in 2 the coordinate water molecules form the 1D chains of [Ni(4,4′‐bpy)(H2O)4] which are H‐bonded to the guest H2O molecules and aminobenzoate anions. The structures of CC 1 and 2 are stabilized into 3D‐supramolecular topology through H bonds and π–π stacking interactions. The nanosized tested compounds 1\ and 2\ are designed to investigate their action on viability and proliferation of five human cancer cell lines. In addition, ABTS assay and rate erythrocyte hemolysis were used to test the antioxidant activity of the nanosized 1\ and 2\. Also, the coordination complexes 1\ and 2\ exhibit good antimicrobial activity keeping them as promising drug candidates for the treatment of bacterial and fungal infections.
Two kinds of polyaniline fiber photo sensor with interdigital electrode and flexible hydrogel
Authors: Zhang Ying , Tao Yulun , Wang Kequan , Zhao Shuai , Zhu Jinbo , Cheng Hao
Published: March 2021

In previous studies, polyaniline nanofiber sensor on interdigital electrode is sensitive to light. Herein, we prepared a flexible hydrogel sensor with polyaniline nanofiber as the active material and polyacrylamide hydrogel as the flexible substrate. Comparing the properties of above two different kinds of sensors with polyaniline nanofiber, the photocurrent generated by PANI‐hydrogel sensor under external light stimulation is about 1 ~ 2 orders of magnitude higher than interdigital electrode sensor, indicating the PANI‐hydrogel sensor is more sensitive. The two sensors can all respond to different wavelengths of monochromatic light, especially sensitive to light of smaller wavelengths such as ultraviolet light (380 nm) and blue light (475 nm). Moreover, the volt‐ampere characteristic curve in response to external light stimulation can be clearly distinguished only when the appropriate concentration of proton acid is doped (3 g citric acid, 7 g acetic acid, and 3 ml HCl).