bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese natural compound decreases pacemaking of rabbit cardiac sinoatrial cells by targeting second messenger regulation of f-channels
Authors: Piantoni Chiara , Paina Manuel , Molla David , Liu Sheng , Bertoli Giorgia , Jiang Hongmei , Wang Yanyan , Wang Yi , Wang Yi , DiFrancesco Dario , Barbuti Andrea , Bucchi Annalisa , Baruscotti Mirko
Published: March 2022

Tongmai Yangxin (TMYX) is a complex compound of the Traditional Chinese Medicine (TCM) used to treat several cardiac rhythm disorders; however, no information regarding its mechanism of action is available. In this study we provide a detailed characterization of the effects of TMYX on the electrical activity of pacemaker cells and unravel its mechanism of action. Single-cell electrophysiology revealed that TMYX elicits a reversible and dose-dependent (2/6 mg/ml) slowing of spontaneous action potentials rate (−20.8/–50.2%) by a selective reduction of the diastolic phase (−50.1/–76.0%). This action is mediated by a negative shift of the If activation curve (−6.7/–11.9 mV) and is caused by a reduction of the cyclic adenosine monophosphate (cAMP)-induced stimulation of pacemaker channels. We provide evidence that TMYX acts by directly antagonizing the cAMP-induced allosteric modulation of the pacemaker channels. Noticeably, this mechanism functionally resembles the pharmacological actions of muscarinic stimulation or β-blockers, but it does not require generalized changes in cytoplasmic cAMP levels thus ensuring a selective action on rate. In agreement with a competitive inhibition mechanism, TMYX exerts its maximal antagonistic action at submaximal cAMP concentrations and then progressively becomes less effective thus ensuring a full contribution of If to pacemaker rate during high metabolic demand and sympathetic stimulation.
Potential role of KRAB-ZFP binding and transcriptional states on DNA methylation of retroelements in human male germ cells
Authors: Fukuda Kei , Makino Yoshinori , Kaneko Satoru , Shimura Chikako , Okada Yuki , Ichiyanagi Kenji , Shinkai Yoichi
Published: March 2022

DNA methylation, repressive histone modifications, and PIWI-interacting RNAs are essential for controlling retroelement silencing in mammalian germ lines. Dysregulation of retroelement silencing is associated with male sterility. Although retroelement silencing mechanisms have been extensively studied in mouse germ cells, little progress has been made in humans. Here, we show that the Krüppel-associated box domain zinc finger proteins are associated with DNA methylation of retroelements in human primordial germ cells. Further, we show that the hominoid-specific retroelement SINE-VNTR-Alus (SVA) is subjected to transcription-directed de novo DNA methylation during human spermatogenesis. The degree of de novo DNA methylation in SVAs varies among human individuals, which confers significant inter-individual epigenetic variation in sperm. Collectively, our results highlight potential molecular mechanisms for the regulation of retroelements in human male germ cells.
The Value of Conceptual Mental Spaces in Structuring a Man as (Endagera) Food in Ekegusii
Authors: Ondara Ntabo Victor , Ogola Onyango James , Ng’arua Ndiritu Nelson
Published: March 2022

Food is useful in the transference of semantic aspects that are vital in the construction of masculinity in society. Consequently, foodsemic metaphors that aid in the conceptualization of omosacha (a man) are pervasive in Ekegusii. Metaphor use may, however, present difficulties in comprehension due to the various interpretations that may be assigned to each of them. The meaning of Ekegusii foodsemic metaphors may, therefore, be elusive to the native speakers of Ekegusii. The paper employs the principle of conceptual mental spaces to interpret Ekegusii foodsemic metaphor within the Cognitive Linguistics framework. The study adopts descriptive research design. First, the terms that are used to describe men in Ekegusii are identified by administering an interview schedule to 48 Ekegusii native respondents purposively sampled on the basis of gender. The data collected is then subjected to the Metaphor Identification Procedure Vrije Universiteit (MIPVU) in which four annotators are used to identify Ekegusii male metaphors. Through the MIPVU, 52 metaphors are identified. The paper then selects one metaphor that describes a man as food hence the Ekegusii foodsemic metaphor for this study. The research reveals that the integration of the four conceptual mental spaces that include two input spaces, the generic space and the blended space is resourceful in structuring a man as a symbol of nourishment in Ekegusii. Moreover, the MIPVU is unveiled as a useful metaphor identification method that provides a clear guide in the establishment of precise metaphors for study. The study concludes that metaphors are integral components of communication and should be explained using the Cognitive Linguistics paradigm. The findings of the study will contribute to Linguistics especially the field of Cognitive Linguistics which is relatively new and has not been subjected to extensive research. In addition, the findings will be useful to metaphor scholars in comprehending Ekegusii male metaphors and culture.
Measuring Outcomes of Interprofessional Education: A Validation Study of the Self-Assessment of Collaboration Skills Measure
Authors: Braathen Kaja
Published: March 2022

Increased attention is being focused on the need for interprofessional collaboration between professional actors, in various fields. In turn, this creates a demand for validated, context-neutral instruments to measure outcomes of interprofessional education. The initial validation of one such measure, the Self-Assessment of Collaboration Skills (SACS) measure, has shown promising results in this regard. The aim of this article has been to contribute to the validation process of the SACS measure by presenting the results of a cross-validation of the measure in a sample of Norwegian students (N= 499) attending a children and youth-focused IPE programme. The study's findings both indicated that the measure is quite stable across the different settings and supported the claim that the SACS is a context-neutral instrument—one that is well-suited to measuring collaboration skills in various IPE settings. These findings may prove important for professionals seeking to evaluate IPE programmes with broad study profiles.
Novel decorating behaviour of silk retreats in a challenging habitat
Authors: Aceves-Aparicio Alfonso , McLean Donald James , Wild Zoe , Schneider Jutta M. , Herberstein Marie E.
Published: March 2022

Many ecological interactions of spiders with their potential prey and predators are affected by the visibility of their bodies and silk, especially in habitats with lower structural complexity that expose spiders. For instance, the surface of tree trunks harbours relatively limited structures to hide in and may expose residents to visual detection by prey and predators. Here we provide the first detailed description of the novel retreat building strategy of the tree trunk jumping spider Arasia mullion. Using fields surveys, we monitored and measured over 115 spiders and 554 silk retreats. These spiders build silk retreats on the exposed surface of tree trunks, where they remain as sedentary permanent residents. Furthermore, the spiders decorate the silk retreats with bark debris that they collect from the immediate surrounding. We discuss the role of silk decoration in the unusual sedentary behaviour of these spiders and the potential mechanisms that allow A. mullion to engineer their niche in a challenging habitat.
Bird protection treatments reduce bird-window collision risk at low-rise buildings within a Pacific coastal protected area
Authors: De Groot Krista L. , Wilson Amy G. , McKibbin René , Hudson Sarah A. , Dohms Kimberly M. , Norris Andrea R. , Huang Andrew C. , Whitehorne Ivy B. J. , Fort Kevin T. , Roy Christian , Bourque Julie , Wilson Scott
Published: March 2022

Background

In North America, up to one billion birds are estimated to die annually due to collisions with glass. The transparent and reflective properties of glass present the illusion of a clear flight passage or continuous habitat. Approaches to reducing collision risk involve installing visual cues on glass that enable birds to perceive glass as a solid hazard at a sufficient distance to avoid it.

Methods

We monitored for bird-window collisions between 2013 and 2018 to measure response to bird protection window treatments at two low-rise buildings at the Alaksen National Wildlife Area in Delta, British Columbia, Canada. After 2 years of collision monitoring in an untreated state, we retrofitted one building with Feather Friendly® circular adhesive markers applied in a grid pattern across all windows, enabling a field-based assessment of the relative reduction in collisions in the 2 years of monitoring following treatment. An adjacent building that had been constructed with a bird protective UV-treated glass called ORNILUX® Mikado, was monitored throughout the two study periods. Carcass persistence trials were conducted to evaluate the likelihood that carcasses were missed due to carcass removal between scheduled searches.

Results and Conclusions

After accounting for differences in area of glass between the two buildings, year, and observer effects, our best-fit model for explaining collision risk included the building’s treatment group, when compared to models that included building and season only. We found that the Feather Friendly® markers reduced collision risk at the retrofitted building by 95%. Collision incidence was also lower at the two monitored façades of the building with ORNILUX® glass compared to the building with untreated glass. Although more research is needed on the effectiveness of bird-protection products across a range of conditions, our results highlight the benefit of these products for reducing avian mortality due to collisions with glass.
The biogeography of bent-toed geckos, Cyrtodactylus (Squamata: Gekkonidae)
Authors: Grismer L. Lee , Poyarkov Nikolay A. , Quah Evan S.H. , Grismer Jesse L. , Wood Jr Perry L.
Published: March 2022

The gekkonid genus Cyrtodactylus is the third largest vertebrate genus on the planet with well over 300 species that range across at least eight biogeographic regions from South Asia to Melanesia. The ecological and morphological plasticity within the genus, has contributed to its ability to disperse across ephemeral seaways, river systems, basins, land bridges, and mountain ranges—followed by in situ diversification within specific geographic areas. Ancestral ranges were reconstructed on a mitochondrial phylogeny with 346 described and undescribed species from which it was inferred that Cyrtodactylus evolved in a proto-Himalaya region during the early Eocene. From there, it dispersed to what is currently Indoburma and Indochina during the mid-Eocene—the latter becoming the first major center of origin for the remainder of the genus that seeded dispersals to the Indian subcontinent, Papua, and Sundaland. Sundaland became a second major center of radiation during the Oligocene and gave rise to a large number of species that radiated further within Sundaland and dispersed to Wallacea, the Philippines, and back to Indochina. One Papuan lineage dispersed west to recolonize and radiate in Sundaland. Currently, Indochina and Sundaland still harbor the vast majority of species of Cyrtodactylus.
Effect of Cavitation Formation on Velocity and Vorticity
Authors: Ferdowsian Espanta
Published: March 2022

In this study, flow in a rectangular shape nozzle has been simulated. Fully hexahedral mesh elements are utilized with having boundary layer mesh in order to avoid excessive mesh destiny in the orifice area. It was found that velocity magnitude, axial velocity and vorticity magnitude increases intensely at the beginning of the orifice area which makes it possible for the cavitation phenomena to occur rapidly. The cavitation that occurs inside diesel fuel injector nozzles has a significant impact on atomization, and modelling this phenomenon will be useful in future injector development. The Schnerr cavitation model was chosen among three distinct cavitation models available in Ansys Fluent v21 because it is capable of properly forecasting choke conditions in cavitating flow. The two-phase flow inside a nozzle is assumed to be a homogenous combination of vapor, liquid, and noncondensable gas in this model. The pressure and velocity profiles derived from the simulations were compared to planar throttle flow experimental findings.
Impact of Parenting Style on Children
Authors: Lhendup Chador
Published: March 2022

The community, and especially the family, affects children’s academic learning. Parents influence children’s current and future learning behaviors. Numerous studies have demonstrated a relationship between parenting style and children’s behavioral problems such as antisocial behaviors and delinquency, so the modification of parenting styles could have a positive impact on the interactions between parents and children. In the literature on children’s learning, parental influence has long been recognized as an important aspect of research, but parent-related factors are mostly unknown. In particular, a factor that can affect parents’ attitudes and children’s views of learning is parenting style. Therefore, this study aims to examine children’s knowledge of learning utilizing a parenting styles’ perspective. The determining role of demographic characteristics in academic learning skills is critical and is investigated in this study. Through interviews, children’s familiarity with parenting style was assessed. Results indicated that older children and those with higher socioeconomic status had better skills in this field. The results also showed that parents could improve their children’s ability of learning by less use of inconsistent discipline and corporal punishments. Parental negligence, contradictory use of corporal punishment, and nonuse of positive behaviors are some factors which are most likely related to children’s outcome of learning. The findings of this study can guide parents and assist relevant authorities to implement policies to more effectively train young children by developing practical and targeted resources.
Effects of Bite Opening on Masseter and Geniohyoid Muscles: A Randomised Clinical Trial
Authors: Abiraj K. R. , Abraham Reji , Mohammed B. N. Abin , Rasool Reyas Y. , Mohammed Fadhil , Ihjas A. C. Mohammed
Published: March 2022

Objective: To evaluate the effects of anterior bite plane on the masseter and geniohyoid muscle thickness.

Materials and Methods: 14 subjects who needed bite opening were allocated as a single group with mean age of 17.4± 3.4 years and mean overbite of 5.3±0.2 was treated with a fixed anterior bite plane (ABT). The pre-treatment (T1) and post-treatment results (T2) was compared to study the effect of Bite opening. The ultrasonographic imaging was used to evaluate masseter muscle thickness (clenched and relaxed) and geniohyoid muscle thickness. 

Results: The study showed, the right masseter muscle thickness (RMT) in (R) at T1 was 8.68 ± 1.13 mm, T2 was 7.68 ± 1.14 mm and in (C) 0.72 ± 1.39 mm and 9.86 ± 1.35 mm respectively While left muscle thickness (LMT) was at 8.54 ± 1.3 mm and 7.68 ± 1.3 mm respectively.  The mean geniohyoid muscle thickness before treatment was 6.58 ±0.69 mm and after treatment was    7.40 ± 0.69 mm with an increase in thickness of 0.8 ±0.04 mm.

Conclusion: Bite opening procedure influence the muscles thickness, with reduction of masseter muscle thickness and increase in geniohyoid muscle thickness.
Use of Natural Products and Their Derivative in Cancer Research for the Discovery of Safer Treatments
Authors: Aldbass Abeer M.
Published: March 2022

Cancer stands as the second leading cause of death after cardiovascular disease worldwide. Many new techniques and procedures have been made in the treatment and control of cancer progression, but many deficiencies and challenges are still being faced. Chemotherapy is normally used for cancer treatment all over the world but it has many undesired side effects like fatigue, hair loss, frequent infection, and anemia. Cancer cells lose some regulatory functions resulting in continued division, which makes cancer cells susceptible to chemotherapeutic drugs. New biomedical tools for safer treatments for this disease are badly needed to improve cancer incidence in the human population. Systemic drug discovery launched a big collection of useful chemotherapeutic agents but toxicities like myotoxicity cardiotoxicity, renal toxicity, pulmonary toxicity, etc. are problematic issues. Natural therapies, derived from plants can decrease such side effects. With the help of animal models, many natural products are being explored and used to treat cancer all over the world. Animal models of cancer can mimic the disease in terms of morphology, biochemistry, and genetics could be helpful to identify the mechanism by which this disease develops in humans. Natural compounds have gained much attention as many compounds have shown very promising anti-cancer properties in vitro, but have yet to be evaluated in humans. In this review, we compile some natural anticancer drugs which are in clinical trials.
Pharmacist Intervention and Medication Errors at DHQ Hospital Bannu KP, Pakistan
Authors: Rani Surayia Shahab , Khan Fahim Ullah , Khan Hidayat Ullah , Ullah Najeeb , Shah Mir Sadiq , Rehman Jamil Ur , Mangi Autif Hussain , Younis Muhammad Nasir , Irfan Hafiz Muhammad
Published: March 2022

Deaths related to drug errors are common in Pakistan, but these are not accurately reported. Since medication management is the main responsibility of nurses, it is vital that they have a good understanding of high alert of medication error. Patient health care, particularly drug fortification, is the main exertion and the challenge for healthcare professionals around the world. The profession of a pharmacist is world-renowned for providing medical care to patients. Herein, we aim to assess the role of pharmacist according to medications error in Government sectors hospitals located in district Bannu Kp Pakistan.

We collected a total number of 368 outdoor prescriptions from July 2011 to December 2011 from District Head Quarter Hospital, Bannu (DHQB). We found 71% of drug-drug interactions (DDIs), 32% of inapt dosage faults and 35% of management errors among them. Male patients with angina pectoris and myocardial infarction had a higher MEs ratio than female patients. According to the findings, clinical pharmacists in hospital wards must provide prompt counseling to primary care doctors during the prescription process, as well as management recommendations to nursing staff and other auxiliary medical employees.
EFEITOS DOS DENTIFRÍCIOS CLAREADORES SOBRE A ESTRUTURA DENTÁRIA: REVISÃO DE LITERATURA ACTION OF CLEANING TOOTHPASTES ON TEETH: LITERATURE REVIEW
Authors: Bahia Modesto Raissa , Silva Marques Gildeon , Maia Barreto de Oliveira Viviane
Published: March 2022

Muitos indivíduos encontram-se insatisfeitos com a cor atual dos seus dentes e neste contexto, destaca-se a busca por dentes brancos e por produtos caseiros capazes de produzir um clareamento dentário eficaz. Entre estes produtos, estão disponíveis no mercado os dentifrícios clareadores com diversos princípios ativos, compostos por diversas substâncias que utilizado em associação com a escova dental, têm por finalidade remover depósitos exógenos aderidos aos dentes e, em alguns casos, prometem remover o escurecimento interno. Diante da relevância do tema, o objetivo dessa revisão bibliométrica foi esclarecer qual a ação dos dentifrícios clareadores sobre as estruturas dentárias e identificar os principais componentes presentes nos principais dentifrícios de venda livre. A metodologia consta de uma pesquisa realizada na base de dados Pubmed, Scielo, Periódico Capes, Medline e Bireme entre os anos de 2008 a 2018, utilizando as palavras chave dentifrício, cremes dentais clareadores, abrasivos, dente e sua tradução para o Inglês. De acordo com a presente revisão, observa-se que os dentifrícios clareadores possuem ação clareadora benéfica limitada e que o uso indiscriminado dos dentifrícios associado à ação mecânica da escova dental pode aumentar os riscos de desenvolvimento de lesões sobre a estrutura dentária, portanto precisam ser utilizados com moderação.  Many individuals are dissatisfied with the current color of their teeth and in this context, the search for white teeth and home-made products capable of producing effective tooth whitening stands out. Among these products are available on the market the whitening toothpastes with various active ingredients, composed of various substances that used in combination with the toothbrush, have the purpose of removing exogenous deposits adhered to the teeth and, in some cases, promise to remove internal darkening. Given the relevance of the theme, the aim of this bibliometric review was to clarify the action of whitening toothpastes on dental structures and to identify the main components present in the main open-air dentifrices. The methodology consists of a research conducted in the database Pubmed, Scielo, Periodical Capes, Medline and Bireme from 2008 to 2018, using the keywords dentifrice, whitening toothpastes, abrasives, tooth and its translation into English. According to the present review, it is observed that whitening toothpastes have limited beneficial whitening action and that the indiscriminate use of toothpastes associated with the mechanical action of the toothbrush can increase the risk of developing lesions on the tooth structure, so they need to be used. with moderation.
RESINAS BULK-FILL: UMA NOVA REALIDADE PARA A RESTAURAÇÃO EM DENTES POSTERIORES BULK-FILL RESIN: A NEW REALITY FOR POSTERIOR TEETH RESTORATION
Authors: Filadelfo Silva Marcelo
Published: March 2022

A restauração de dentes posteriores, realizada com o uso de resinas compostasdiretas têm se mostrado desafiadora, tendo em vista as dificuldadesinerentes à técnica operatória, relacionada a inserção, fotoativaçãoe sua relação com fatores críticos como contração de polimerização eo estresse que pode produzir tensão na interface dente/restauração ea prevenção à microinfiltração marginal, causadora de falha e insucessoem muitas situações clinicas. Com o intuito de tornar este procedimentomais prático, a introdução de novos materias na rotina clínica, como asresinas bulk fill nas formulações de alta ou baixa viscosidade, requeremum amplo conhecimento de suas propriedades físicas, característicasmecânicas, citotóxicas, e de aplicação clínica, visando assim sua maiorlongevidade. O presente estudo de revisão revelou que compósitos bulkfill, comparados aos convencionais, são promissores, permitindo seu usoem incrementos maiores, mantendo suas propriedades mecânicas favoráveisapós a fotoativação, bem como adequada biocompatibilidade.Outra constatação foi as melhores propriedades de polimerização comograu de conversão e profundidade de polimerização verificadas nos compósitosbulk fill na consistência fluida, frente aos demais materiais resinososconvencionais ou mesmo as resinas bulk fill de alta viscosidade.É consenso nos estudos avaliados que pesquisas de acompanhamentoclínico devem ser realizadas para um maior conhecimento deste materialem função na cavidade oral.The restoration of posterior teeth, carried out with the use of direct compositeresins, has proved challenging, considering the difficulties inherentto the operative technique, related to insertion, photoactivation and itsrelationship with critical factors such as polymerization contraction andthe stress it can produce tension in the tooth / restoration interface andthe prevention of marginal microleakage, which causes failure and failurein many clinical situations. In order to make this procedure more practical, the introduction of new materials in the clinical routine, such as bulkfill resins in high or low viscosity formulations, requires a wide knowledgeof their physical properties, mechanical characteristics, cytotoxic, andclinical application, thus aiming at its greater longevity. The present reviewstudy revealed that bulk fill composites, compared to conventionalones, are promising, allowing their use in larger increments, maintainingtheir favorable mechanical properties after photoactivation, as well as adequatebiocompatibility. Another finding was the better polymerizationproperties such as degree of conversion and depth of polymerization verifiedin bulk fill composites in fluid consistency, compared to other conventionalresinous materials or even high viscosity bulk fill resins. Thereis a consensus in the studies evaluated that clinical follow-up researchshould be carried out for a better understanding of this material, dependingon the oral cavity.
A photoreceptor with characteristics of phytochrome triggers sporulation in the true slime mould Physarum polycephalum
Authors: Starostzik Christine , Marwan Wolfgang
Published: July 2002

Phytochrome is a ubiquitous photoreceptor in plants that controls a variety of responses to light, including gene expression, differential cell growth and intracellular movement of organelles. All phytochromes analysed so far are reversibly interconverted by light between an inactive and an active conformation, each of which has a different and characteristic absorbance spectrum. Based on photophysiological measurements we provide evidence, that a photoreceptor with these unique properties of phytochrome triggers sporulation in the true slime mould Physarum polycephalum.
Dynamics and density of mitochondria‐rich cells in toad skin epithelium
Authors: Katz Uri , Gabbay Shoshana
Published: July 2002

Summary— The dynamics of change in mitochondria‐rich (MR) cells density in the skin epithelium of Bufo viridis was studied on skin biopsies taken in vivo, throughout experimental periods lasting up to 3 months. When the bathing solution contained Cl−, MR cells' density (Dmrc) greatly decreased. There was one exception, when the acclimation solution was KCl, Dmrc in the skin increased. The rate of decrease in Dmrc depended on the mode of acclimation. When bath NaCl concentration was elevated slowly in small increments, the change in Dmrc was very slow. A regression line was calculated for the rate of decrease in the density of MR cells. An equation in the form of y = 1574–10.23x (where x = days; R2 = 0.626) was obtained with bath NaCl that was elevated from 30 to 200 mmol/l, in 45 days. Oxytocin (60 mU/ml) increased sodium transport, independently and without effect on Cl− conductance. Theophylline (1 mmol/l), which leads also to elevation of cellular cAMP in contrast, increased Na+ transport, but elevated Cl− conductance 3–4 times as well. Cl− conductance that is activated by transepithelial potential was much lower in skin from hyperosmotic NaCl‐acclimated toads, as compared with that in skin from tap water‐acclimated animals. Our experiments confirm that MR cells are a major pathway for Cl− conductance, as suggested earlier. However, the density of these cells in the skin epithelium of B viridis depends not only on bath NaCl concentration, but also on the mode of acclimation of the animals. Since transport functions other than gCl reside in the amphibian skin MR cells, the density of MR cells must also depend on these functions. These functions, and the mechanisms responsible for the down and up regulation of MR cells' density, remain to be established.
A lyso‐platelet activating factor phospholipase C, originally suggested to be a neutral‐sphingomyelinase, is located in the endoplasmic reticulum
Authors: Neuberger Yael , Shogomori Hidehiko , Levy Zehava , Fainzilber Michael , Futerman Anthony H.
Published: July 2002

Recently a putative mammalian neutral‐sphingomyelinase was cloned [Tomiuk et al. (1998) Proc. Natl. Acad. Sci. USA 95, 3638–3643; GenBank accession number AJ222801]. We have overexpressed this enzyme in cultured cells and demonstrate, using four different tagged constructs, that it is localized at the endoplasmic reticulum and not at the plasma membrane. This localization precludes a role for enzyme AJ222801 in the sphingomyelin cycle. Furthermore, a recent publication demonstrated that this enzyme has lyso‐platelet activating factor (PAF) phospholipase C activity [Sawai et al. (1999) J. Biol. Chem. 274, 38131–38139]. Together, these data suggest a role for enzyme AJ222801 in the regulation of PAF metabolism.
MOMP (major outer membrane protein) of Campylobacter jejuni; a versatile pore‐forming protein
Authors: Dé Emmanuelle , Jullien Magali , Labesse Gilles , Pagès Jean Marie , Molle Gérard , Bolla Jean Michel
Published: July 2002

The great majority of trimeric porins of Gram‐negative bacteria cannot be dissociated into monomers without disrupting their folded conformation. The porin of Campylobacter jejuni, however, displays two folded structures, a classical oligomer and a monomer resistant to detergent denaturation. We probed the transition of trimer to monomer using light scattering experiments and examined the secondary structures of these two molecular states by infra‐red spectroscopy. The channel‐forming properties of both trimer and monomer were studied after incorporation into artificial lipid bilayers. In these conditions, the trimer induced ion channels with a conductance value of 1200 pS in 1 M NaCl. The pores showed marked cationic selectivity and sensitivity to low voltage. Analysis of the isolated monomer showed nearly the same single‐channel conductance and the same selectivity and sensitivity to voltage. These results indicate that the folded monomer form of C. jejuni MOMP displays essentially the same pore‐forming properties as the native trimer.
Regulatory role of the 3′ untranslated region of luteinizing hormone receptor: effect on mRNA stability
Authors: Nair Anil K , Menon K.M.J
Published: July 2002

Posttranscriptional regulation of luteinizing hormone receptor (LHR) mRNA has a significant role in regulating cell surface receptor expression during ovarian cycle. In order to gain insight into the mechanism of posttranscriptional regulation, the cis‐acting elements in the 3′ untranslated region (3′ UTR) of LHR mRNA were examined by transfection studies followed by measurements of the receptor expression and receptor mRNA half‐life. The results show that the inhibitory effect exerted by the 3.51 kb 3′ UTR of the LHR resides in the distal 1.98 kb region. Half‐life measurement of LHR mRNA showed that the inhibitory effect of the 3′ UTR was due to a decrease in receptor mRNA stability. Deletion studies revealed that the entire 1.98 kb region is required for LHR mRNA destabilization. Although the 3.51 kb 3′ UTR of LHR contains 11 AUUUA motifs, their removal had no effect on mRNA stability or receptor expression. Thus, although AUUUA motifs have been implicated in mRNA stability, these motifs do not appear to play an inhibitory role in LHR expression. The 3′ UTR of LHR was also able to decrease the expression of a reporter gene indicating that the inhibitory effect of 3′ UTR is not unique to the open reading frame of LHR. The present studies show that the distal 1.98 kb portion of the 3′ UTR exerts an inhibitory effect on the expression of LHR by decreasing the receptor mRNA half‐life. The inhibitory effect of 3′ UTR might play a role in the maintenance of the steady state levels of the receptor mRNA under different physiological states.
The three‐dimensional structure of human transaldolase
Authors: Thorell Stina , Gergely Peter , Banki Katalin , Perl Andras , Schneider Gunter
Published: July 2002

The crystal structure of human transaldolase has been determined to 2.45 Å resolution. The enzyme folds into an α/β barrel structure and is thus similar in structure to other class I aldolases. Structure‐based sequence alignment of available sequences of the transaldolase subfamily reveals that eight active site residues are invariant in the whole subfamily. Other invariant residues are mainly involved in the formation of the hydrophobic core of the enzyme. Noteworthy is a hydrophobic cluster consisting of five invariant residues. Human transaldolase has been implicated as an autoantigen in multiple sclerosis and four immunodominant peptide segments are located at the surface of the enzyme, accessible to autoantibodies.
Breast milk – immunomodulatory signals against allergic diseases
Authors: Hoppu Ulla , Kalliomäki Marko , Laiho Kirsi , Isolauri Erika
Published: July 2002

Breastfeeding holds a key position with regard to the increasing burden of allergic diseases in the industrialized countries. Not only does it provide the infant with nutrients for growth and development, it also confers immunological protection during a critical period in life, when the infant's own defense mechanisms are immature. A delicate balance of stimulatory, even inflammatory, maturational signals, together with a myriad of anti‐inflammatory compounds, is transferred from mother to infant via breastfeeding. Breastfeeding mothers, however, do not constitute a uniform group. The composition of breast milk shows marked individual variation and so, consequently, does the success of breastfeeding in reducing the risk of disease. Recent clinical studies indicate that the potential of breastfeeding to counteract allergic disease may be promoted by dietary means. While uncoordinated elimination diets result in a risk of general nutritional inadequacy or deficiency of essential single nutrients, a balanced diet following current dietary recommendations, specifically containing fresh fruits and vegetables (antioxidants) and fat of predominantly vegetable origin, may be associated with a lower incidence of atopy in the infant. As early nutrition appears to program the subsequent health of the child, the importance of the maternal dietary composition during breastfeeding should be emphasized. In future, an improved understanding of the mechanisms of this programming may offer specific therapeutic modalities for the prevention of allergic disease.
Synthesis, biological activity, and solution structures of a cyclic dodecapeptide from the EGF‐2 domain of blood coagulation factor VII
Authors: Hu C.‐K. , Llinás M. , Agner K.E. , Örning L. , Sakariassen K.S. , Fischer P.M.
Published: July 2002

Abstract: The cyclic dodecapeptide, disulfide‐cyclo‐[H‐Cys‐Val‐Asn‐Glu‐Asn‐Gly‐Gly‐Cys(Acm)‐Glu‐Gln‐Tyr‐Cys‐OH], which corresponds to the 91–102 sequence of the second epidermal growth factor domain of human blood coagulation factor VII, was synthesized using solid‐phase procedures. It was shown to be an inhibitor at the key step in the induction of coagulation by the extrinsic pathway, i.e. the factor VII/tissue factor‐catalyzed activation of coagulation factor X. The solution structure of this peptide was investigated by NMR spectroscopy and was computer‐modeled via molecular mechanics. Structures were calculated based on 112 distance and nine dihedral angle constraints. The resulting backbone structures were classified into two structural subsets: one which exhibited a twisted ‘8’‐shaped folding and another describing an open, circular ‘O’ outline. The local backbone structures of segments Asn3‐Glu4‐Asn5, Gly7‐Cys8 and Gln10‐Tyr11 were well preserved among the two subsets. Apart from the unrestrained N‐ and C‐termini, Gly6 and Glu9 sites exhibited marked local disorder between the two subsets, suggesting localized flexible hinges likely to govern tertiary structure interconversion between the two subsets. Two transient hydrogen bonds were identified from pH chemical shift titrations by matching the pKa values of NH and carboxylate groups, which supported the occurrence of the ‘8’ structure, and agreed with temperature coefficients of peptidyl NH resonances. Structure−function relationships of the peptide were discussed in terms of the likely physiological function of the disulfide‐bonded loop in factor VII which the peptide represents.
Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity
Authors: NOVO Carlos , FARNAUD Sebastien , TATA Renée , CLEMENTE Alda , BROWN Paul R.
Published: July 2002

The aliphatic amidase from Pseudomonas aeruginosa belongs to the nitrilase superfamily, and Cys166 is the nucleophile of the catalytic mechanism. A model of amidase was built by comparative modelling using the crystal structure of the worm nitrilase—fragile histidine triad fusion protein (NitFhit; Protein Data Bank accession number 1EMS) as a template. The amidase model predicted a catalytic triad (Cys-Glu-Lys) situated at the bottom of a pocket and identical with the presumptive catalytic triad of NitFhit. Three-dimensional models for other amidases belonging to the nitrilase superfamily also predicted Cys-Glu-Lys catalytic triads. Support for the structure for the P. aeruginosa amidase came from site-direct mutagenesis and from the locations of amino acid residues that altered substrate specificity or binding when mutated.
Identification of the two essential groups in the family 3 β-glucosidase from Flavobacterium meningosepticum by labelling and tandem mass spectrometric analysis
Authors: CHIR Jiunly , WITHERS Stephen , WAN Chin-Feng , LI Yaw-Kuen
Published: July 2002

β-Glucosidase from Flavobacterium meningosepticum (Fbgl) catalyses the hydrolysis of β-1,4-glucosidic bonds via a two-step double-displacement mechanism in which two amino acid residues act as nucleophile and acid/base catalyst. Definitive identification of these two residues is provided by the two active-site-directed inactivators, 2′,4′-dinitrophenyl-2-deoxy-2-fluoro-β-d-glucoside (2FDNPG) and N-bromoacetyl-β-d-glucosylamine (NBGN), which stoichiometrically label the nucleophile and the acid/base catalyst of Fbgl, respectively. Pseudo-first-order inactivation rate constants (ki) of 0.25±0.01 and 0.05±0.01min−1 and dissociation constants (Ki) of 90±15 and 4.4±0.2mM are determined for 2FDNPG and NBGN, respectively. Proteolytic digestion of the labelled proteins, followed by peptide mapping and tandem MS analysis identify Asp-247 and Glu-473 as the catalytic nucleophile and acid/base residues, respectively, of Fbgl. This study confirms that the catalytic nucleophile of family 3 glycohydrolase is conserved across sub-families. However, different sub-families may have unique general acid/base catalysts.
Proinflammatory mediator activity, endogenous antagonists and the systemic inflammatory response in intra-abdominal sepsis
Authors: Wakefield C H , Barclay G R , Fearon K C H , Goldie A S , Ross J A , Grant I S , Ramsay G , Howie J C
Published: July 2002

Background

Severe intra-abdominal sepsis continues to carry a high mortality rate. The physiological response to sepsis in this condition and its relationship with proinflammatory mediators and their endogenous antagonists require further clarification.

Methods

Fifty-seven patients were stratified by Acute Physiology And Chronic Health Evaluation (APACHE) II score at the time of admission to an intensive care unit (group 1, score of less than 20; group 2, score of 20 or more). Serial measurements of clinical and immunological variables were made.

Results

Non-survivors from group 2 had a raised acute physiology score (P = 0·01), a higher peak serum interleukin (IL) 6 concentration (P = 0·03) and a depressed level of endogenous immunoglobulin (Ig) G class antiendotoxin core antibody (P = 0·005). In group 1, although organ failure score increased progressively in non-survivors, physiology score and peak IL-6 level were similar to those in survivors, and endogenous IgG class antiendotoxin core antibody titre rose (P = 0·02). In both groups IL-1 and tumour necrosis factor α were detected infrequently, but their natural antagonists were present in much higher concentrations in both survivors and non-survivors. Levels of C-reactive protein were raised in both but were not significantly different between survivors and non-survivors.

Conclusion

During the development of organ failure and death, the pattern of proinflammatory mediators and their endogenous antagonists can vary markedly and may in part be determined by the extent of the initial physiological disturbance.
Postoperative weight gain after standard Whipple's procedure versus pylorus-preserving pancreatoduodenectomy: the influence of tumour status
Authors: van Berge Henegouwen M I , Moojen T M , van Gulik T M , Rauws E A J , Obertop H , Gouma D J
Published: July 2002

Background

Recent reports suggest a better postoperative weight gain after pylorus-preserving pancreatoduodenectomy (PPPD) compared with standard pancreatoduodenectomy (PD). Factors that could also influence postoperative weight gain, such as tumour-positive resection margins and tumour recurrence, have not been taken into account in these studies. The aim of this prospective study was to evaluate weight gain in the first 15 months after PD or PPPD and to investigate the influence of other tumour-related factors.

Methods

From 1991 to 1995, 140 patients underwent subtotal pancreatoduodenectomy; 125 patients underwent resection for malignant disease of the pancreatic head region (56 had PD and 69 PPPD). Patients' weights were evaluated in the pre-illness phase, before operation and during four postoperative phases (at 3, 7, 11 and 15 months). Weight was calculated as a percentage of the pre-illness weight. Patients were subdivided according to tumour status: PD with positive and PD with negative tumour status; PPPD with positive and PPPD with negative tumour status. Tumour-positive status was defined as either microscopically tumour-positive resection margins or radiologically or cytologically proven tumour recurrence within 2 years of surgery.

Results

Five patients died during the hospital stay (PD, four; PPPD, one) (overall mortality rate 4 per cent). There was no difference in overall weight gain between patients having PD and PPPD. There was, however, a difference in patients with positive and negative tumour status for PD (P = 0·0003) and PPPD (P < 0·0001).

Conclusion

There is only a minimal difference in postoperative weight gain between patients having PD and PPPD. Differences in postoperative weight gain are related more to positive resection margins and tumour recurrence than to the type of resection.
Annales de Chirurgie
Authors: Castaing D
Published: July 2002

Dr Denis Castaing, Editor of Annales de Chirurgie, chooses the best from issues eight, nine and ten of 1997. A reciprocal digest written by our European Editor, Mr Colin Johnson, is published in the French journal.
Association of 5′ CpG demethylation and altered chromatin structure in the promoter region with transcriptional activation of the multidrug resistance 1 gene in human cancer cells
Authors: Kusaba Hitoshi , Nakayama Masaharu , Harada Taishi , Nomoto Minoru , Kohno Kimitoshi , Kuwano Michihiko , Wada Morimasa
Published: July 2002

Selection of human cells for resistance to vincristine or doxorubicin often induces overexpression of the multidrug resistance 1 gene (MDR1), which encodes the cell surface P‐glycoprotein, as a result of gene amplification or transcriptional activation. However, the precise mechanism underlying such transcriptional activation of MDR1 remains unclear. The relation between methylation status of CpG sites in the MDR1 promoter region and transcriptional activation of MDR1 has now been investigated. The P‐glycoprotein‐overexpressing, multidrug‐resistant KB/VJ300 and KB‐C1 cells, which were established from human cancer KB3‐1 cells, were examined; MDR1 is transcriptionally activated but not amplified in KB/VJ300 cells, whereas it is amplified in KB‐C1 cells. Determination of the methylation status revealed that the MDR1 promoter region was hypomethylated in KB/VJ300 and KB‐C1 cells, but hypermethylated in KB3‐1 cells. Prior treatment of KB3‐1 cells with the DNA methyltransferase inhibitor 5‐aza‐2′‐deoxycytidine resulted in a 90‐fold increase in the frequency of vincristine‐resistance. Of three lines, KB/CdR‐1, KB/CdR‐2, and KB/CdR‐3, established from KB3‐1 cells after exposure to 5‐aza‐2′‐deoxycytidine, MspI/HpaII sites in the MDR1 promoter region were hypomethylated in KB/CdR‐1 and KB/CdR‐2 cells, but not in KB/CdR‐3 cells. MDR1 mRNA expression was detected in KB/CdR‐1 and KB/CdR‐2 cells, but not in KB/CdR‐3 cells. The binding of YB‐1 and Sp1, transcription factors implicated in MDR1 expression, in the MDR1 promoter was not affected by the methylation status of a neighboring CpG sites. The MDR1 promoter region in KB/VJ300 cells showed an increased sensitivity to DNase I compared with that in KB3‐1 cells, suggesting an altered chromatin structure. The methylation status of the promoter region may plays an important role in MDR1 overexpression and in acquisition of the P‐glycoprotein‐mediated multidrug resistance phenotype.
Screening for gestational diabetes; past, present and future
Authors: Hanna F. W. F. , Peters J. R.
Published: July 2002

Gestational diabetes is carbohydrate intolerance, with onset or first recognition of hyperglycaemia during pregnancy. Several studies have suggested that gestational hyperglycaemia is associated with adverse maternal and fetal outcomes, promoting the case for screening. Conversely, others argue that screening for gestational diabetes may colour the clinical judgement, influencing further management, e.g. more ‘unjustified’ caesarean sections. Additionally, the lack of definitive data either on a clear‐cut glycaemic threshold for the development of adverse outcomes or on the impact of intervention is emphasized by opponents of screening. This review attempts to evaluate the available data on screening for gestational diabetes. Oral glucose tolerance test is promoted on the basis that the diabetogenic stress of pregnancy is encountered during late gestation and is best recognized in the fed state. There are different tests, including the 1 h/50‐g, 2 h/75‐g and 3 h/100‐g tests, with practical limitations, including the time and cost involved and the unpleasant supra‐physiological glucose load that is unrelated to body weight, and issues of reproducibility and sensitivity/specificity profiles. Despite its convenience, the poor sensitivity of random glucose has precluded its routine use for screening. Fasting glucose appears to be promising but further testing is required to ensure satisfactory sensitivity/specificity in different populations. Despite its limitations, the oral glucose tolerance test has become established as the ‘most acceptable’ diagnostic test for gestational diabetes. More convenient methods, e.g. fasting or random or post‐load glucose, have to be validated therefore against the oral glucose tolerance test to gain acceptance for routine screening.

Diabet. Med 19, 351–358 (2002)
Weight of edged lenses in different eyewire shapes and sizes
Authors: Tang Churk‐Yan
Published: July 2002

Weights of edged lenses in different eyewire shapes and sizes were studied through mathematically generated eyewire shapes. The patterns of weight variation are often regular and predictable. The relation of lens weight changes in neighbouring sizes of a given eyewire shape and that in different boxed vertical lens dimensions of a given general eyewire appearance were established. These results were verified with physically edged lenses. Through these relations, it will be possible to predict the amount of weight change in a pair of spectacles upon changing the frame size and in some cases of eyewire shape modification.