bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinction between HCO3−‐ and CO2‐dependent photosynthesis in the cyanobacterium Synechococcus leopoliensis based on the selective response of HCO3− transport to Na+
Authors: Miller A.G. , Canvin D.T.
Published: July 2002

At low concentrations of dissolved inorganic carbon (DIC) at pH 8.0 the rates of DIC transport and fixation by Synechococcus leopoliensis were markedly stimulated by the addition of Na+ Carbonic anhydrase (CA) addition gave similar results. The Na+‐stimulated photosynthesis was inhibited by Li+ whereas the CA‐stimulated photosynthesis was not. The addition of a high DIC concentration (1 mM) overcame the need for either Na+ or CA. We suggest that Na+ stimulated HCO3
− transport whereas CA stimulated CO2 transport (by increasing the supply rate of CO2 to the cells).
Calcium‐activated calcium permeability in parathyroid cells
Authors: Gylfe Erik , Larsson Rolf , Johansson Hans , Nygren Peter , Rastad Jonas , Wallfelt Chris , Åkerström Göran
Published: July 2002

The Ca2+ receptor mechanism of the parathyroid cell was studied using La3+ as a probe. La3+ was found to bind to the cell surface without further penetration. Measurements of 45Ca fluxes and the cytoplasmic Ca2+ concentration (Cai
2+) revealed a stimulatory component in the action of La3+ on Ca2+ permeability resulting in a rise in Cai
2+ These effects mimicked those obtained when raising the extracellular Ca2+ concentration from 0.5 to 3.0 mM, but the actions of La3+ and Ca2+ were not additive. The results suggest the existence of a novel Ca2+ permeability physiologically activated by binding of Ca2+ to an external receptor.
Activation of protein kinase C inhibits prostaglandin‐ and potentiates adenosine receptor‐stimulated accumulation of cyclic AMP in a human T‐cell leukemia line
Authors: Nordstedt Christer , Jondal Mikael , Fredholm Bertil B.
Published: July 2002

Accumulation of cAMP in the human T‐cell leukemia cell line Jurkat was stimulated by the adenosine analogue 5′‐N‐ethylcarboxamidoadenosine (NECA) and by prostaglandin E2, (PGE2). Addition of two phorbol esters, PDiBu and TPA, markedly enhanced the NECA‐stimulated accumulation of cAMP whereas the PGE2‐stimulated cAMP accumulation was substantially reduced. The non‐tumor‐promoting phorbol ester, 4α‐PDD, had no effect on either NECA‐ or PGE2‐stimulated cAMP accumulation. The ability of PDiBu to inhibit the effect of PGE2 and to stimulate the effect of NECA remained in the presence a low concentration of forskolin (0.3 μM), which per se increased both NECA‐ and PGE2‐stimulated cAMP accumulation. Our results suggest that the effect of PK‐C‐activating drugs on receptor‐mediated cAMP accumulation is entirely dependent on which receptor is being stimulated
Repression and reactivation of the variant surface glycoprotein gene in Trypanosoma brucei
Authors: Ehlers Bernhard , Czichos Joachim , Overath Peter
Published: July 2002

Rapid repression of variant surface glycoprotein (VSG) synthesis is an early event during the in vitro transformation of Trypanosoma brucei from coated bloodstream forms to uncoated procyclic cells. Repression occurs at the transcriptional level and is triggered by the combined action of two signals: a reduction in temperature from 37 to 27°C and the addition of the citric acid cycle intermediates citrate and cis‐aconitate. It is shown that synthesis of VSG mRNA can be reactivated up to 8 h after triggering differentiation by releasing either one or both of the signals. After 30 h repression is irreversible. The results suggest that transformation of bloodstream forms to procyclic cells proceeds through a reversible phase to an irreversible committed state. A reversible repression of VSG mRNA synthesis is also observed upon inhibition of protein synthesis in bloodstream forms at 37°C.
Adenosine 3′,5′‐cyclic monophosphate (cAMP) inhibits phorbol ester‐induced growth of an IL‐2‐dependent T cell line
Authors: Goto Yuso , Takeshita Toshikazu , Sugamura Kazuo
Published: July 2002

We previously established a human T cell line, TPA‐Mat, which can proliferate in response to not only interleukin‐2 (IL‐2), but also phorbol esters such as 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and phorbol‐12,13‐dibutyrate (PDBu). The present study demonstrated that the PDBu‐dependent growth of TPA‐Mat cells was inhibited up to 90% by adenosine 3′,5′‐cyclic monophosphate (cAMP) raising agents such as forskolin, cholera toxin and 1‐methyl‐3‐isobutylxanthine, and cAMP analogues, whereas the IL‐2‐stimulated TPA‐Mat growth was slightly inhibited. These findings suggest that the signal transduction pathway of PDBu‐induced growth, which should involve activation of protein kinase C, is sensitive to cAMP, and that it cannot be exactly identical to the signal transduction pathway of Il‐2‐induced growth in TPA‐Mat cells.
Identification of the human hepatic microsomal glucose‐6‐phosphatase enzyme
Authors: Burchell Ann , Waddell Ian D. , Countaway Janice L. , Arion William J. , Hume Robert
Published: July 2002

The glucose‐6‐phosphatase enzyme protein of the human hepatic microsomal glucose‐6‐phosphatase system was identified as a 36.5 kDa polypeptide. The 36.5 kDa glucose‐6‐phosphatase enzyme protein was shown to be absent in the microsomes isolated from a patient previously diagnosed as having a type 1a glycogen storage disease.
Comment: mitochondrial genes and cancer
Authors: Hadler Herbert I.
Published: July 2002

Mitochondrial DNA; Carcinogenesis
Identification of α2‐ and α3‐subunits of the GABAA‐benzodiazepine receptor complex purified from the brains of young rats
Authors: Fuchs K. , Adamiker D. , Sieghart W.
Published: July 2002

Polyclonal antibodies were raised to synthetic amino acid sequences of the bovine GABAA receptor α2‐ and α3‐subunits and purified by affinity chromatography on a column coupled with the respective peptide. Anti‐peptide α2(416–424) and anti‐peptide α3(459–467) antibodies immunoprecipitated GABAA receptors and recognized a protein of 53 kDa (P53) and 59 kDa (P59), respectively, in Western blots of GABAA receptors purified from the brains of 5–10 day old rats. P53 as well as P59 are specifically photolabeled by [3H]flunitrazepam and are recognized by the α‐subunit specific monoclonal antibody bd 28.
Electrogenic pump current of sarcoplasmic reticulum Ca2+‐ATPase reconstituted at high lipid/protein ratio
Authors: Cornelius Flemming , Møller Jesper V.
Published: July 2002

When Ca2+‐ATPase from sarcoplasmic reticulum was reconstituted with excess phospholipid (at a 1:800 weight ratio) in a monomeric state and activated by Ca2+ and ATP a transmembrane potential developed which could be continuously recorded by the fluorochrome oxonol VI. The results demonstrate the electrogenicity or active Ca2+ transport during continuous turnover. The fluorescence signal can be quantified in terms of net current electrical flow through the vesicular membranes and compared to the ATP hydrolysis to give the number of electrostatic charges transferred during Ca2+ transport. From such measurements a stoichiometry of 1.8±0.4 Ca2+ per ATP hydrolysed at pH 7.1 can be obtained. The method is also convenient for determination of the kinetics of Ca2+‐ATPase activation by ATP and free Ca2+.
Expression analysis of ruminant α‐lactalbumin in transgenic mice: Developmental regulation and general location of important cis‐regulatory elements
Authors: Soulier S. , Vilotte J.L. , Stinnakre M.G. , Mercier J.C.
Published: July 2002

The bovine α‐lactalbumin transgene with 750 bp and 336 bp of the 5′ and 3′ flanking region, respectively, is developmentally regulated as its endogenous counterpart in transgenic mice. Comparative expression analysis of three 5′‐shortened constructs suggests that the region −4771/−220 contains important cis‐acting transcriptional elements. The level of expression of a long caprine α‐lactalbumin transgene encompassing 8.5 kb and 9.5 kb of the 5′ and 3′ flanking region, respectively, was higher but still unrelated to the copy number. Expression of the transgenes and of endogenous milk‐protein genes was tissue‐specific. In contrast with a recent report, only low amounts of the relevant mRNA were detected in some skin samples, which suggests a possible contamination by mammary tissue.
Cloning and expression of a bovine adenosine A1 receptor cDNA
Authors: Tucker Amy L. , Linden Joel , Robeva Anna S. , D'Angelo Drew D. , Lynch Kevin R.
Published: July 2002

A bovine brain adenosine A1 receptor cDNA encoding a 326 amino acid protein has been identified. This cDNA, which encodes a protein >90% identical to analogous rat and dog receptors, was transiently expressed in COS‐1 cells. Recombinant receptors exhibited the features of bovine A1 receptors that distinguish it from rat and canine receptors, including subnanomolar K
i for 1,3‐dipropyl‐8‐cyclopentylxanthine, R‐phenylisopropyl‐adenosine (R‐PIA) and xanthine amino conjugate, and the distinct potency order: R‐PIA >
S‐PIA > 5′‐N‐ethylcarboxamidoadenosine > 2′‐chloroadenosine. The results indicate that the pharmacological differences between A1 adenosine receptors among species result from only minor differences in receptor structures.
Membrane‐bound annexin V isoforms (CaBP33 and CaBP37) and annexin VI in bovine tissues behave like integral membrane proteins
Authors: Bianchi Roberta , Giambanco Ileana , Ceccarelli Paolo , Pula Grazia , Donato Rosario
Published: July 2002

The distribution of annexin V isoforms (CaBP33 and CaBP37) and of annexin VI in bovine lung, heart, and brain subfractions was investigated with special reference to the fractions of these proteins which are membrane‐bound. In addition to EGTA‐extractable pools of the above proteins, membranes from lung, heart, and brain contain EGTA‐resistant annexins V and VI which can be solubilized with detergents (Triton X‐100 or Triton X‐114). A strong base like Na2CO3, which is usually effective in extracting peripheral membrane proteins, only partially solubilizes the membrane‐bound, EGTA‐resistant annexins analyzed here. Also, only 50–60% of the Triton X‐114‐soluble annexins partition in the aqueous phase, the remaining fractions being recovered in the detergent‐rich phase. Altogether, these findings suggest that, by an as yet unknown mechanism, following Ca2+‐dependent association of annexin V isoforms and annexin VI with membranes, substantial fractions of these proteins remain bound to membranes in a Ca2+‐independent way and behave like integral membrane proteins. These results further support the possibility that the above annexins might play a role in membrane trafficking and/or in the regulation of the structural organization of membranes.
Occurrence and sequence of a DnaJ protein in plant (Allium porrum) epidermal cells
Authors: Bessoule J.-J.
Published: July 2002

Antibodies raised against a purified fraction from microsomal membranes of leek epidermal cells were used to screen a λzap expression library from epidermal cells of leek plants. A near full‐length clone was isolated. This cDNA contains an open reading‐frame of 1,191 bp coding for a DnaJ protein (leek DNAJ 1 or LDJ1). Leek DnaJ1 represents the second protein of this type described in a pluricellular organism, the first being that sequenced from human cells.
A major cellular substrate for protein kinases, annexin II, is a DNA‐binding protein
Authors: Boyko V. , Mudrak O. , Svetlova M. , Negishi Y , Ariga H. , Tomilin N.
Published: July 2002

We have screened a human cDNA expression library in λgt11 for clones encoding Alu‐binding proteins using direct binding of labeled Alu DNA to recombinant phage lysates fixed on a membrane, and isolated a clone 98% identical in sequence to the well‐known substrate of protein kinases, annexin II, which was suggested earlier to play a role in transduction of mitogenic signals and DNA replication. A diagnostic property of annexins is their binding to phospholipids in the presence of calcium ions, and we have found that the interaction of proteins of human nuclear extracts with Alu subsequences is suppressed by Ca/phosphatidylserine liposomes, suggesting overlapping of Ca/phospholipid‐ and DNA‐binding domains in annexin II.
JAK3 Janus kinase is involved in interleukin 7 signal pathway
Authors: Zeng Yi-Xin , Takahashi Hiroshi , Shibata Masao , Hirokawa Katsuiku
Published: July 2002

Interleukin (IL) 7 is an important cytokine regulating both T and B cell development and inducing the formation of lymphokine‐activated killer cells and cytolytic T lymphocytes. This study reports the role of JAK family kinases in the IL‐7 signalling pathway in a T cell clone. The results have shown that out of 4 members of JAK family tyrosine kinases (JAK1, JAK2, JAK3 and Tyk2), only JAK3 was tyrosine‐phosphorylated and activated in cells of a T cell clone by stimulation with IL‐7. Furthermore, STAT1α (STAT, the signal transducers and activators of transcription) and p44 of MAPK (mitogen‐activated protein kinases) were tyrosine phosphorylated by IL‐7 stimulation, indicating that the two signal pathways might be involved in IL‐7 signal transduction.
Nonsense mutations in the vpr gene of HIV‐1 during in vitro virus passage and in HIV‐1 carrier‐derived peripheral blood mononuclear cells
Authors: Nakaya Takaaki , Fujinaga Koh , Kishi Masahiko , Oka Shinichi , Kurata Takeshi , Jones Ian M. , Ikuta Kazuyoshi
Published: July 2002

Long‐term, persistent infection by HIV‐1 is a prerequisite for the development of AIDS. However, little is known of the determinants required for HIV‐1 to cause persistence. We have reported previously that persistent infection of a T cell line by a cytopathogenic strain of HIV‐1 became increasingly likely with in vitro serial passage of the virus. DNA sequencing of the persistent strains revealed a nonsense mutation in the vpr gene in all isolates tested. Here, we report the development and use of a semi‐quantitative PCR method to detect the vpr nonsense mutation within populations of virus. Our results show that vpr mutants also arise in cells during acute infection and increase progressively with serial passage of the virus. In addition, HIV‐1‐seropositive individuals were examined and found to carry the same vpr nonsense mutation at high frequency in virus‐infected PBMC. These data are consistent with a mechanism of HIV‐1 persistence in vivo and in vitro in which virus cytopathogenic potential is lost by the build up of nonsense mutations in vpr.
An Arabidopsis thaliana cDNA encoding PS II‐X, a 4.1 kDa component of photosystem II: a bipartite presequence mediates SecA/ΔpH‐independent targeting into thylakoids
Authors: Soo Jung Kim  , Robinson David , Robinson Colin
Published: July 2002

Higher plant photosystem II preparations contain a 4.1 kDa polypeptide (subunit X) associated with the oxygen‐evolving core complex. We describe the isolation of a cDNA encoding PS II‐X from Arabidopsis thaliana, in which the C‐terminal region is highly homologous to partially sequenced PS II‐X from wheat and spinach. The mature protein of 42 residues is preceded by a 74‐residue, bipartite presequence similar to those involved in the targeting of nuclear‐encoded thylakoid lumen proteins, although hydrophobicity analysis indicates the presence of a single transmembrane span in the mature protein. Moreover, import of pre‐PS II‐X into the thylakoid membrane of isolated chloroplasts is unaffected by inhibitors of either the Sec‐ or ΔpH‐dependent thylakoidal protein translocases, suggesting a spontaneous insertion mechanism. PS II‐X appears to be encoded as a mature protein by the plastid genome in the chlorophyll a
+
c‐containing alga, Odontella sinensis. We thus propose that the thylakoid transfer signal of Arabidopsis pre‐PS II‐X represents a recent acquisition, in phylogenetic terms, compared with signals of Sec‐dependent lumenal proteins.
Molecular modelling of human gastric alcohol dehydrogenase (class IV) and substrate docking: differences towards the classical liver enzyme (class I)
Authors: Moreno Alberto , Farrés Jaume , Parés Xavier , Jörnvall Hans , Persson Bengt
Published: July 2002

A three‐dimensional model of the human class IV alcohol dehydrogenase has been calculated based upon the X‐ray structure of the class I enzyme. As judged from the model, the substrate‐binding site is wider than in class I, compatible with the differences in substrate specificities and the large difference in K
m value for ethanol. Substrate docking performed for the class I structure and the class IV model show all‐trans‐retinol and 11‐cis‐retinol to bind better to the class IV enzyme. The calculations also indicate that 16‐hydroxyhexadecanoic acid binds in a different manner for the two enzyme classes. A simulation of coenzyme‐binding indicates that the adenine ring of the coenzyme might be differently bound in class IV than in class I, decreasing the interactions with Asp‐223 which is compatible with the higher k
cat values for class IV.
Tetanus immunization and prenatal care in developing countries
Authors: Buekens P. , Tsui A. , Kotelchuck M. , Degraft‐Johnson J.
Published: July 2002

Objective: We sought to estimate the proportion of women immunized against tetanus while attending prenatal care in the developing countries. Method: We computed the ratio of the percentage of births to women immunized against tetanus to the percentage of births to women with prenatal care (TP ratio). A TP ratio is lower than 100% if not every woman attending prenatal care is immunized. We used 1986–1992 Demographic and Health Surveys data from 38 countries. Results: The mean TP ratios were 86% in Africa (n = 23), 79% in Asia (n = 6) and 60% in Latin America and the Caribbean (n = 9). The TP ratio was lower than 75% in 15 countries. Of these, four had a TP ratio lower than 50%. Conclusion: In many countries the number of pregnant women immunized against tetanus is lower than the number of women attending prenatal care, suggesting that prenatal services are missing opportunities to immunize attending women.
Designing dementia treatment studies: Diagnosis, efficacy criteria, and duration
Authors: Spiegel R , Irwin P
Published: July 2002

Development of treatments for dementia is beset by special problems in defining the diagnosis, establishing efficacy criteria, and specifying the necessary duration of study. There is need for agreement among clinicians and scientists on diagnostic subgroups of dementia. Similarly, there is a need for harmonization of the regulatory guidelines in Europe, Japan, and the United States regarding the decision set of variables on which to base efficacy claims. The duration of trials must be based upon the intended claim: transient symptomatic benefit, maintained symptomatic benefit, or a therapeutic effect on disease progression. Claims other than transient benefit require long-term trials, suggested to be of at least six months in duration. Problems with long-term studies include slow patient accrual, high dropout rates, changing milieu, low return on investment, and lack of unanimity regarding regulatory requirements. Regulatory authorities must come to some accord, consonant with current clinical/scientific wisdom and consensus, regarding diagnosis, efficacy criteria, and feasible study duration, in order to attract continued sponsor investment in the development of antidementia treatments.
Announcing the winner of the IJGO Prize Paper Award for 2000 Award article
Authors: Saraçoglu F , Sahin I , Eser E , Göl K , Türkkani B
Published: July 2002

Objective: To investigate the variations of nucleated red blood cell (NRBC) counts in acute and chronic fetal hypoxia and to examine if it could be possible to establish a cutoff value for the number of NRBCs for prediction of fetal acidosis. Method: We prospectively studied 77 pregnant women. Patients were grouped as acute (n=11) and chronic fetal distress (n=21) and controls (n=45). At delivery the umbilical cord was double clamped and blood samples were collected. Results: The mean NRBC counts in chronic fetal distress group was higher than acute fetal distress. NRBC counts were found to be correlated with umbilical cord pH (r=−0.57; P<0.001). The cutoff value predicting fetal acidosis was determined as 14/100 leukocytes (sensitivity 87%, specificity 81%) by using ROC analysis. Conclusion: The duration and the severity of fetal asphyxia may be predicted by the number of NRBCs per leukocyte.
Thrombocytopenia, hypertension and seizures in eclampsia
Authors: Gracia P. Vigil‐De , García‐Cáceres E.
Published: July 2002

Objective: Mortality by eclampsia most likely relies on factors that are associated with seizures, but not directly related to them. The objective of the current study is to analyze these probable factors. Method: This study evaluates patients with eclampsia only. Age, parity, weeks of gestation, blood pressure, platelet counts and cause of death were analysed. The groups of survivors and fatalities were compared using relative risk (RR) with 95% confidence intervals (CI), χ2 and Student's t‐test. Results: A total of 446 cases of eclampsia were studied, of which there were 371 survivors and 75 deaths. The incidence was 14.2/10000 births with mortality of 14.4%. Mortality was more frequent in patients over 25 years of age (P < 0.005). The diastolic blood pressure showed significant difference between the survivor and fatality group (P < 0.05). Before convulsion, thrombocytopenia was present in 148 patients (33.2%) of which 95 survived and 53 died (RR = 2.76; 95% CI 2.20–3.46; P < 0.0000001). Conclusions: Mortality by eclampsia is directly related to age, diastolic blood pressure ≥110 mmHg, seizure and thrombocytopenia. Our findings suggest poor maternal prognosis if seizures occur associated with thrombocytopenia.
Multidentate, V‐Shaped Pyridine Building Blocks as Tectons for Crystal Engineering
Authors: Guagnini Francesca , Pedrini Alessando , Dalcanale Enrico , Massera Chiara
Published: December 2020

The formation of supramolecular structural units through self‐assembly is a powerful method to design new architectures and materials endowed with specific properties. With the aim of adding a group of versatile tectons to the toolkit of crystal engineers, we have devised and synthesised four new V‐shaped building blocks characterised by an aryl acetylene scaffold comprising three substituted pyridine rings connected by two triple bonds. The judicious choice of different substituents on the pyridine rings provides these tectons with distinctive steric, electrostatic and self‐assembly properties, which influence their crystal structures and their ability to form co‐crystals. Co‐crystals of the tectons with tetraiododifluorobenzene were obtained both via traditional and mechanochemical crystallisation strategies, proving their potential use in crystal engineering. The energetic contributions of the supramolecular interactions at play in the crystal lattice have also been evaluated to better understand their nature and strength and to rationalise their role in designing molecular crystals.
Concentration‐Dependent Self‐Assembly of an Unusually Large Hexameric Hydrogen‐Bonded Molecular Cage
Authors: Merget Severin , Catti Lorenzo , Zev Shani , Major Dan T. , Trapp Nils , Tiefenbacher Konrad
Published: December 2020

The sizes of available self‐assembled hydrogen‐bond‐based supramolecular capsules and cages are rather limited. The largest systems have volumes of approximately 1400–2300 Å3. Herein, we report a large, hexameric cage based on intermolecular amide–amide dimerization. The unusual structure with openings, reminiscent of covalently linked cages, is held together by 24 hydrogen bonds. With a diameter of 2.3 nm and a cavity volume of ∼2800 Å3, the assembly is larger than any previously known capsule/cage structure relying exclusively on hydrogen bonds. The self‐assembly process in chlorinated, organic solvents was found to be strongly concentration dependent, with the monomeric form prevailing at low concentrations. Additionally, the formation of host–guest complexes with fullerenes (C60and C70) was observed.
Mediated Generation of Conjugate Acid by UV and Blue Sensitizers with Upconversion Nanoparticles at 980 nm
Authors: Oprych Dennis , Strehmel Bernd
Published: December 2020

NIR and UV exposure of systems comprising upconversion nanoparticles (UCNP) based on NaYF4:Tm/Yb@NaYF4, a sensitizer absorbing either in the blue or UV region, and an onium salt with weak coordinating anion resulted in formation of conjugate acid (con‐H+). That was namely Ivocerin (di(4‐methoxybenzoyl)diethylgermane), ITX (2‐iso‐propyl thioxanthone), anthracene, pyrene, rubrene, camphore quinone, and a strong fluorescent coumarin (1,1,6,6,8‐pentamethyl‐2,3,5,6‐tetrahyhdro‐1H,4H‐11‐oxa‐3a‐aza‐benzo[de]anthracene‐10‐one). Quantification occurred by treatment with Rhodamine B lactone whose color switched to intensive red after photolytic formation of con‐H+. Exposure with a NIR laser at 980 nm resulted in less con‐H+ compared to 395 nm where all sensitizers absorb radiation. UCNP did not mainly interfered formation of con‐H+. The different rates obtained in both experiments responsibly explain the failure and success to initiate polymerization of epoxides applying ether 980 nm or 395 nm excitation, respectively.
Aromatic Metamorphosis of Thiophenes by Means of Desulfurative Dilithiation
Authors: Kaga Atsushi , Iida Hirokazu , Tsuchiya Shun , Saito Hayate , Nakano Koji , Yorimitsu Hideki
Published: December 2020

A new mode of aromatic metamorphosis has been developed, which allows thiophenes and their benzo‐fused derivatives to be converted to a variety of exotic heteroles. This transformation involves 1) the efficient generation of key 1,4‐dianions by means of desulfurative dilithiation with lithium powder and 2) the subsequent trapping of the dianions with heteroatom electrophiles in a one‐pot manner. Via the desulfurative dilithiation, the sulfur atoms of thiophenes are replaced also with a carbon–carbon double bond or a 1,2‐phenylene for the construction of benzene rings.
Big data and machine learning framework for clouds and its usage for text classification
Authors: Pintye István , Kail Eszter , Kacsuk Péter , Lovas Róbert
Published: December 2020

Reference architectures for big data and machine learning include not only interconnected building blocks but important considerations (among others) for scalability, manageability and usability issues as well. Leveraging on such reference architectures, the automated deployment of distributed toolsets and frameworks on various clouds is still challenging due to the diversity of technologies and protocols. The paper focuses particularly on the widespread Apache Spark cluster with Jupyter as the particularly addressed framework, and the Occopus cloud‐agnostic orchestrator tool for automating its deployment and maintenance stages. The presented approach has been demonstrated and validated with a new, promising text classification application on the Hungarian academic research infrastructure, the OpenStack‐based MTA Cloud. The paper explains the concept, the applied components, and illustrates their usage with real use‐case measurements.
Body mass and hibernation microclimate may predict bat susceptibility to white‐nose syndrome
Authors: Haase Catherine G. , Fuller Nathan W. , Dzal Yvonne A. , Hranac C. Reed , Hayman David T. S. , Lausen Cori L. , Silas Kirk A. , Olson Sarah H. , Plowright Raina K.
Published: December 2020

In multihost disease systems, differences in mortality between species may reflect variation in host physiology, morphology, and behavior. In systems where the pathogen can persist in the environment, microclimate conditions, and the adaptation of the host to these conditions, may also impact mortality. White‐nose syndrome (WNS) is an emerging disease of hibernating bats caused by an environmentally persistent fungus, Pseudogymnoascus destructans. We assessed the effects of body mass, torpid metabolic rate, evaporative water loss, and hibernaculum temperature and water vapor deficit on predicted overwinter survival of bats infected by P. destructans. We used a hibernation energetics model in an individual‐based model framework to predict the probability of survival of nine bat species at eight sampling sites across North America. The model predicts time until fat exhaustion as a function of species‐specific host characteristics, hibernaculum microclimate, and fungal growth. We fit a linear model to determine relationships with each variable and predicted survival and semipartial correlation coefficients to determine the major drivers in variation in bat survival. We found host body mass and hibernaculum water vapor deficit explained over half of the variation in survival with WNS across species. As previous work on the interplay between host and pathogen physiology and the environment has focused on species with narrow microclimate preferences, our view on this relationship is limited. Our results highlight some key predictors of interspecific survival among western bat species and provide a framework to assess impacts of WNS as the fungus continues to spread into western North America.
A context analysis of bobbing and fin‐flicking in a small marine benthic fish
Authors: Santon Matteo , Deiss Felix , Bitton Pierre‐Paul , Michiels Nico K.
Published: December 2020

Most antipredator strategies increase survival of individuals by signaling to predators, by reducing the chances of being recognized as prey, or by bewildering a predator's perception. In fish, bobbing and fin‐flicking are commonly considered as pursuit‐deterrent behaviors that signal a predator that it has been detected and thus lost its surprise‐attack advantage. Yet, very few studies assessed whether such behavioral traits are restricted to the visual presence of a predator. In this study, we used the yellow black‐headed triplefin Tripterygion delaisi to investigate the association between these behaviors and the visual exposure to (a) a black scorpionfish predator (Scorpaena porcus), (b) a stone of a size similar to that of S. porcus, (c) a conspecific, and (d) a harmless heterospecific combtooth blenny (Parablennius sanguinolentus). We used a laboratory‐controlled experiment with freshly caught fish designed to test for differences in visual cues only. Distance kept by the focal fish to each stimulus and frequency of bobbing and fin‐flicking were recorded. Triplefins kept greater distance from the stimulus compartment when a scorpionfish predator was visible. Bobbing was more frequent in the visual presence of a scorpionfish, but also shown toward the other stimuli. However, fin flicks were equally abundant across all stimuli. Both behaviors decreased in frequency over time suggesting that triplefin become gradually comfortable in a nonchanging new environment. We discuss why bobbing and fin‐flicking are not exclusive pursuit‐deterrent behaviors in this species, and propose additional nonexclusive functions such as enhancing depth perception by parallax motion (bobbing) or signaling vigilance (fin‐flicking).
The De Winter‐like electrocardiogram pattern in inferior and lateral leads associated with left circumflex coronary artery occlusion
Authors: Chen Qingxing , Zou Tian , Pang Yang , Ling Yunlong , Zhu Wenqing
Published: December 2020

The aim of this report was to investigate coronary artery occlusion related to De Winter‐like electrocardiogram (ECG) pattern. A patient admitted to Zhongshan Hospital who was diagnosed with acute coronary syndrome with De Winter‐like ECG pattern was reviewed in our case report. In this case, we found that a De Winter‐like ECG change in the inferior and lateral leads was associated with left circumflex coronary artery occlusion. After a timely reperfusion therapy, the symptom was obviously alleviated with a normalization of upsloping ST‐segment. Doctors should be aware that De Winter‐like ECG changes can also predict acute occlusion in any coronary artery, not only in the left anterior descending artery and right coronary artery but also in the left circumflex coronary artery.
On the N‐Arylation of Acetamide Using 2‐, 3‐ and 1’‐Substituted Iodoferrocenes**
Authors: Kadari Lingaswamy , Erb William , Halauko Yury S. , Ivashkevich Oleg A. , Matulis Vadim E. , Lyakhov Dmitry , Roisnel Thierry , Radha Krishna Palakodety , Mongin Florence
Published: December 2020

Various 2‐, 3‐ and 1’‐substituted iodoferrocenes were reacted with acetamide in the presence of copper(I) iodide (1 equiv), N,N’‐dimethylethylenediamine (1 equiv), tripotassium phosphate (2 equiv) in dioxane at 90 °C for 14 h, and allowed a large range of original 1,2‐, 1,3‐ and 1,1’‐disubstituted ferrocenes to be obtained. The results were compared as a function of the substituent and its position on the ring. DFT calculations revealed higher activation barrier for the oxidative addition in the ferrocene series when compared with classical planar aromatics. Structure‐property relationships were applied to rationalize the reactivity of the different iodoferrocenes.
Reactions of a 3‐Phenyl‐1‐trifluoromethyl‐prop‐2‐yne Iminium Salt with Furans, Thiophenes, and Pyrroles
Authors: Schneider Thomas , Heinrich Georg , Koch Raphael , Maas Gerhard
Published: December 2020

Reactions of a novel propyne iminium salt, N,N‐dimethyl 3‐phenyl‐1‐trifluoromethyl‐propyne iminium triflate, with electron‐rich heteroaromatic ring systems (furans, thiophenes, pyrroles) are reported. The 1‐CF3‐propyne iminium ion can act as a highly reactive ambident electrophile, giving rise to simple electrophilic heteroaromatic ring substitution products, and as a 1,3‐biselectrophile leading to C2+C3‐CF3 annulation products. Moreover, it is an electron‐deficient alkyne which was found to afford double [2+2] cycloaddition products with 2,5‐dimethylfuran and 2,5‐dimethylthiophene. The obtained molecular structures include CF3‐containing compounds with cyclopenta[b]furan, cyclopenta[b]thiophene, cyclopenta[c]thiophene, cyclopenta[b]pyrrole, cyclopenta[c]pyrrole, 3H‐pyrrolizine, and 1,4‐dihydrocyclopenta[b]pyrrole ring systems. Analogous reactions of 1,3(or 1,4)‐phenylenebis(1‐CF3‐propyne iminium) salts with furans, pyrroles or thiophenes in a 2 : 1 stoichiometry lead to phenylene‐tethered condensed heterocycles of the same type.
Harnessing the power of electrophoresis and chromatography: Offline coupling of reverse phase liquid chromatography‐capillary zone electrophoresis‐tandem mass spectrometry for analysis of host cell proteins in monoclonal antibody producing CHO cell line
Authors: Kumar Ramesh , Shah Rohan L. , Ahmad Shadab , Rathore Anurag S.
Published: December 2020

Host cell proteins (HCPs) are widely regarded as a critical quality attribute for a biotherapeutic product. Bottom up MS is the present gold standard for HCP analysis but suffers from incomplete protein identification due to complex nature of the HCP mixture and limited separation efficiency of the preceding LC‐based systems. In this paper, we present for the first time an application involving use of LC‐CE‐MS/MS platform for analysis of HCPs. It has been demonstrated that the proposed platform has been able to successfully identify 397 HCPs from the supernatants of recombinant Chinese hamster ovary cells, twice and thrice the number of proteins identified by the state‐of‐the‐art LC‐MS/MS (189 HCPs) and CE‐MS/MS (128 HCPs) analyses, respectively. Of these, 225 HCPs were unique to the LC‐CE‐MS/MS approach and were not identified by either LC‐MS/MS or CE‐MS/MS. It is observed that the LC‐CE‐MS/MS platform combines the benefits of LC‐MS/MS and CE‐MS/MS techniques and identifies peptides in a wider range of size, pI, and hydrophobicity. Additionally, LC‐CE‐MS/MS also identified more HCPs associated with cellular components, molecular functions, biological processes, peptidases, and secretory proteins. The proposed approach would thus be a useful addition in HCP analysis and secretome studies of mAb‐producing Chinese hamster ovary cells.
New insights on the ventral attention network: Active suppression and involuntary recruitment during a bimodal task
Authors: Solís‐Vivanco Rodolfo , Jensen Ole , Bonnefond Mathilde
Published: December 2020

Detection of unexpected, yet relevant events is essential in daily life. fMRI studies have revealed the involvement of the ventral attention network (VAN), including the temporo‐parietal junction (TPJ), in such process. In this MEG study with 34 participants (17 women), we used a bimodal (visual/auditory) attention task to determine the neuronal dynamics associated with suppression of the activity of the VAN during top‐down attention and its recruitment when information from the unattended sensory modality is involuntarily integrated. We observed an anticipatory power increase of alpha/beta oscillations (12–20 Hz, previously associated with functional inhibition) in the VAN following a cue indicating the modality to attend. Stronger VAN power increases were associated with better task performance, suggesting that the VAN suppression prevents shifting attention to distractors. Moreover, the TPJ was synchronized with the frontal eye field in that frequency band, indicating that the dorsal attention network (DAN) might participate in such suppression. Furthermore, we found a 12–20 Hz power decrease and enhanced synchronization, in both the VAN and DAN, when information between sensory modalities was congruent, suggesting an involvement of these networks when attention is involuntarily enhanced due to multisensory integration. Our results show that effective multimodal attentional allocation includes the modulation of the VAN and DAN through upper‐alpha/beta oscillations. Altogether these results indicate that the suppressing role of alpha/beta oscillations might operate beyond sensory regions.
Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive‐stage small cell lung cancer: A multicentre, randomised, double‐blind, placebo‐controlled Phase II trial
Authors: Daniel Davey , Kuchava Vladimer , Bondarenko Igor , Ivashchuk Oleksandr , Reddy Sreekanth , Jaal Jana , Kudaba Iveta , Hart Lowell , Matitashvili Amiran , Pritchett Yili , Morris Shannon R. , Sorrentino Jessica A. , Antal Joyce M. , Goldschmidt Jerome
Published: December 2020

Trilaciclib is an intravenous CDK4/6 inhibitor administered prior to chemotherapy to preserve haematopoietic stem and progenitor cells and immune system function from chemotherapy‐induced damage (myelopreservation). The effects of administering trilaciclib prior to carboplatin, etoposide and atezolizumab (E/P/A) were evaluated in a randomised, double‐blind, placebo‐controlled Phase II study in patients with newly diagnosed extensive‐stage small cell lung cancer (ES‐SCLC) (NCT03041311). The primary endpoints were duration of severe neutropenia (SN; defined as absolute neutrophil count <0.5 × 109 cells per L) in Cycle 1 and occurrence of SN during the treatment period. Other endpoints were prespecified to assess the effects of trilaciclib on additional measures of myelopreservation, patient‐reported outcomes, antitumour efficacy and safety. Fifty‐two patients received trilaciclib prior to E/P/A and 53 patients received placebo. Compared to placebo, administration of trilaciclib resulted in statistically significant decreases in the mean duration of SN in Cycle 1 (0 vs 4 days; P < .0001) and occurrence of SN (1.9% vs 49.1%; P < .0001), with additional improvements in red blood cell and platelet measures and health‐related quality of life (HRQoL). Trilaciclib was well tolerated, with fewer grade ≥3 adverse events compared with placebo, primarily due to less high‐grade haematological toxicity. Antitumour efficacy outcomes were comparable. Administration of trilaciclib vs placebo generated more newly expanded peripheral T‐cell clones (P = .019), with significantly greater expansion among patients with an antitumour response to E/P/A (P = .002). Compared with placebo, trilaciclib administered prior to E/P/A improved patients' experience of receiving treatment for ES‐SCLC, as shown by reduced myelosuppression, and improved HRQoL and safety profiles.
Maternal vitamin D, oxidative stress, and pre‐eclampsia
Authors: Wei Shu Qin , Bilodeau Jean‐François , Julien Pierre , Luo Zhong‐Cheng , Abenhaim Haim A. , Bi Wei Guang , Nuyt Anne Monique , Leduc Line , Audibert François , Fraser William D.
Published: December 2020

Objective

To examine the associations between risk of pre‐eclampsia and pregnancy levels of maternal 25‐hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers.

Methods

A nested case–control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F2‐isoprostanes; F2‐isoPs) were measured in plasma at 12–18 and 24–26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L.

Results

Maternal vitamin D deficiency was associated with increased 8‐iso‐PGF2α (P = 0.037), 15(R)‐PGF2α (P = 0.004), (±)5‐iPF2α‐VI (P = 0.026) at 12–18 weeks. Vitamin D deficiency was inversely associated with 8‐iso‐PGF2α (P = 0.019) and (±)5‐iPF2α‐VI isomer (P = 0.010) at 24–26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67–13.75) and increased (±)5‐iPF2α‐VI (aOR, 2.46; 95% CI, 1.16–5.22) at 24–26 weeks were associated with risk of pre‐eclampsia. However, the interaction test between 25(OH)D and (±)5‐iPF2α‐VI was not significant (P = 0.143).

Conclusion

Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F2‐isoP isomers, including the well‐studied marker 8‐iso‐PGF2α. Whether vitamin D‐induced oxidative stress mediates the risk of pre‐eclampsia warrants future study.
[6]‐Gingerol impedes 7,12‐dimethylbenz(a)anthracene‐induced inflammation and cell proliferation‐associated hamster buccal pouch carcinogenesis through modulating Nrf2 signaling events
Authors: Sun Yugang , Ren Jinmin , Wang Fang
Published: December 2020

The present study examines the chemopreventive role of [6]‐gingerol, an active component of ginger, on 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced hamster buccal pouch (HBP) carcinogenesis models. The HBP has been developed with an addition of 0.5% of DMBA to the HBP area three times per week, up to the end of the 16th experimental week. At the end of the experiment, we noticed 100% tumor incidence and precancerous lesions, such as dysplasia, hyperplasia, keratosis, and well‐differentiated squamous cell carcinoma, in DMBA‐induced HBP. Furthermore, we observed that [6]‐gingerol inhibited the increased thiobarbituric acid‐reactive substances and decreased antioxidant levels in DMBA‐induced hamsters. Moreover, [6]‐gingerol inhibits DMBA‐exposed over expression of inflammatory markers (inducible nitric oxide synthase, interleukin [IL]‐1β, IL‐6, cyclooxygenase‐2, and tumor necrosis factor‐α) and cell proliferation markers (cyclin D1, proliferating cell nuclear antigen); induces proapoptotic markers in HBP. Nuclear factor erythroid‐2‐related factor‐2 (Nrf2) is a major antioxidant transcription factor, which regulates the antioxidant gene‐dependent scavenge of tumor proliferation and apoptosis. Overexpression of Nrf2 signaling plays a pivotal role and can be a novel target in preventing carcinogenesis. In this study, [6]‐gingerol restores the DMBA‐induced depletion of Nrf2 signaling and thereby prevents buccal pouch carcinogenesis in hamsters. These results point out that [6]‐gingerol impedes the responses of inflammatory and cell proliferation‐associated progression of cancer through the action of Nrf2 signaling.
Comparative insight into the genomic landscape of SARS‐CoV‐2 and identification of mutations associated with the origin of infection and diversity
Authors: Mishra Divya , Suri Gurparsad Singh , Kaur Gurleen , Tiwari Manish
Published: December 2020

The analyses of 2325 severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) genomes revealed 107, 162, and 65 nucleotide substitutions in the coding region of SARS‐CoV‐2 from the three continents America, Europe, and Asia, respectively. Of these nucleotide substitutions 58, 94, and 37 were nonsynonymous types mostly present in the Nsp2, Nsp3, Spike, and ORF9. A continent‐specific phylogram analyses clustered the SARS‐CoV‐2 in the different group based on the frequency of nucleotide substitutions. Detailed analyses about the continent‐specific amino acid changes and their effectiveness by SNAP2 software was investigated. We found 11 common nonsynonymous mutations; among them, two novel effective mutations were identified in ORF9 (S194L and S202N). Intriguingly, ORF9 encodes nucleocapsid phosphoprotein possessing many effective mutations across continents and could be a potential candidate after the spike protein for studying the role of mutation in viral assembly and pathogenesis. Among the two forms of certain frequent mutation, one form is more prevalent in Europe continents (Nsp12:L314, Nsp13:P504, Nsp13:Y541, Spike:G614, and ORF8:L84) while other forms are more prevalent in American (Nsp12:P314, Nsp13:L504, Nsp13:C541, Spike:D614, and ORF8:L84) and Asian continents (Spike:D614), indicating the spatial and temporal dynamics of SARS‐CoV‐2. We identified highly conserved 38 regions and among these regions, 11 siRNAs were predicted on stringent criteria that can be used to suppress the expression of viral genes and the corresponding reduction of human viral infections. The present investigation provides information on different mutations and will pave the way for differentiating strains based on virulence and their use in the development of better antiviral therapy.
Enhanced growth and yield of oyster mushroom by growth‐promoting bacteria Glutamicibacter arilaitensis MRC119
Authors: Kumari Simpal , Naraian Ram
Published: December 2020

Promotion of mushroom growth by means of biological agents replacing chemicals is an emerging and highly demanded issue in the sector of mushroom cropping. The present study was aimed to search for a novel bacterium potentially able to enhance mushroom growth and yield. A total of 2165 bacterial isolates purified from different samples were scrutinized through various growth‐promoting attributes. As a consequence of rigorous screening, 26 isolates found exhibiting positive traits of mushroom growth promotion. Thereafter, in response to the cocultivation (fungus and bacteria), a potent bacterial strain was isolated capable to improve significantly the mycelial growth. In cocultivation the highest radial and linear growth rate was 7.6 and 8.1 mm/day on 10th and 11th days, respectively. The fruitbody yields and biological efficiency (BE) of the inoculated sets were 28% and 58% higher than the uninoculated control sets. The bacterium was molecularly identified based on 16S ribosomal RNA sequencing and confirmed as Glutamicibacter arilaitensis MRC119. Therefore, the bioinoculant of the current bacterium can be potentially useful as an ecofriendly substitute stimulating the production of mushroom fruit bodies with improved BE.
The combined ratio of estrogen, progesterone, Ki‐67, and P53 to predict the recurrence of endometrial cancer
Authors: Jia Mingzhu , Jiang Peng , Huang Zhen , Hu Jing , Deng Ying , Hu Zhuoying
Published: December 2020

Background and Objectives

We aimed to explore the capacity of the combined ratio of biomarkers to predict the recurrence of Stage I–III endometrial cancer (EC).

Methods

A total of 473 patients were enrolled after screening. The cut‐off value of the ratio was calculated by the receiver operating characteristic curve (ROC). The univariate and multivariate Cox regression analysis was used to assess the correlation between the combined ratio and the recurrence of EC. The differences of clinicopathological parameters between the two groups divided based on the threshold were compared.

Result

The ROC curve showed that 0.92 was the optimal cut‐off value of the ratio ([ER + PR]/[P53 + Ki67]). The multivariate analysis demonstrated that only International Federation of Gynecology and Obstetrics stage (p = .031) and the combined ratio (p = .004) were independent risk factors of recurrence. The 3‐year recurrence‐free survival (RFS) and overall survival of patients in the low‐ratio group were 54.1% and 66.8%, respectively; while in the high‐ratio group were 94.9% and 97.9%, respectively (p < .001). The 3‐year RFS of 194 patients, who did not receive the adjuvant therapy, was 54.7% and 97.2% between two groups (p < .001).

Conclusions

The optimal cut‐off value (0.92) of the combined ratio was demonstrated to be better to predict the recurrence of EC than a single immunohistochemical marker.