bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation and topology of protein interaction networks under duplication-divergence evolution
Authors: Evlampiev Kirill , Isambert Hervé
Published: July 2008

Genomic duplication-divergence processes are the primary source of new protein functions and thereby contribute to the evolutionary expansion of functional molecular networks. Yet, it is still unclear to what extent such duplication-divergence processes also restrict by construction the emerging properties of molecular networks, regardless of any specific cellular functions. We address this question, here, focusing on the evolution of protein–protein interaction (PPI) networks. We solve a general duplication-divergence model, based on the statistically necessary deletions of protein–protein interactions arising from stochastic duplications at various genomic scales, from single-gene to whole-genome duplications. Major evolutionary scenarios are shown to depend on two global parameters only: (
i
) a protein conservation index (
M
), which controls the evolutionary history of PPI networks, and (
ii
) a distinct topology index (
M′
) controlling their resulting structure. We then demonstrate that conserved, nondense networks, which are of prime biological relevance, are also necessarily scale-free by construction, irrespective of any evolutionary variations or fluctuations of the model parameters. It is shown to result from a fundamental linkage between individual protein conservation and network topology under general duplication-divergence evolution. By contrast, we find that conservation of network motifs with two or more proteins cannot be indefinitely preserved under general duplication-divergence evolution (independently from any network rewiring dynamics), in broad agreement with empirical evidence between phylogenetically distant species. All in all, these evolutionary constraints, inherent to duplication-divergence processes, appear to have largely controlled the overall topology and scale-dependent conservation of PPI networks, regardless of any specific biological function.
Host cell recognition by the henipaviruses: Crystal structures of the Nipah G attachment glycoprotein and its complex with ephrin-B3
Authors: Xu Kai , Rajashankar Kanagalaghatta R. , Chan Yee-Peng , Himanen Juha P. , Broder Christopher C. , Nikolov Dimitar B.
Published: July 2008

Nipah virus (NiV) and Hendra virus are the type species of the highly pathogenic paramyxovirus genus
Henipavirus
, which can cause severe respiratory disease and fatal encephalitis infections in humans, with case fatality rates approaching 75%. NiV contains two envelope glycoproteins, the receptor-binding G glycoprotein (NiV-G) that facilitates attachment to host cells and the fusion (F) glycoprotein that mediates membrane merger. The henipavirus G glycoproteins lack both hemagglutinating and neuraminidase activities and, instead, engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors. Here, we report the crystal structures of the NiV-G both in its receptor-unbound state and in complex with ephrin-B3, providing, to our knowledge, the first view of a paramyxovirus attachment complex in which a cellular protein is used as the virus receptor. Complex formation generates an extensive protein–protein interface around a protruding ephrin loop, which is inserted in the central cavity of the NiV-G β-propeller. Analysis of the structural data reveals the molecular basis for the highly specific interactions of the henipavirus G glycoproteins with only two members (ephrin-B2 and ephrin-B3) of the very large ephrin family and suggests how they mediate in a unique fashion both cell attachment and the initiation of membrane fusion during the virus infection processes. The structures further suggest that the NiV-G/ephrin interactions can be effectively targeted to disrupt viral entry and provide the foundation for structure-based antiviral drug design.
Dual Regulation of Mad2 Localization on Kinetochores by Bub1 and Dam1/DASH that Ensure Proper Spindle Interaction
Authors: Saitoh Shigeaki , Kobayashi Yasuyo , Ogiyama Yuki , Takahashi Kohta
Published: July 2008

The spindle assembly checkpoint monitors the state of spindle–kinetochore interaction to prevent premature onset of anaphase. Although checkpoint proteins, such as Mad2, are localized on kinetochores that do not interact properly with the spindle, it remains unknown how the checkpoint proteins recognize abnormalities in spindle–kinetochore interaction. Here, we report that Mad2 localization on kinetochores in fission yeast is regulated by two partially overlapping but distinct pathways: the Dam1/DASH and the Bub1 pathways. We show that Mad2 is localized on “unattached” as well as “tensionless” kinetochores. Our observations suggest that Bub1 is required for Mad2 to detect tensionless kinetochores, whereas Dam1/DASH is crucial for Mad2 to detect unattached kinetochores. In cells lacking both Bub1 and Dam1/DASH, Mad2 localization on kinetochores is diminished, and mitotic progression appears to be accelerated despite the frequent occurrence of abnormal chromosome segregation. Furthermore, we found that Dam1/DASH is required for promotion of spindle association with unattached kinetochores. In contrast, there is accumulating evidence that Bub1 is involved in resolution of erroneous spindle attachment on tensionless kinetochores. These pathways may act as molecular sensors determining the state of spindle association on each kinetochore, enabling proper regulation of the checkpoint activation as well as promotion/resolution of spindle attachment.
p120-Catenin Is a Key Component of the Cadherin–γ-Secretase Supercomplex
Authors: Kiss Alexi , Troyanovsky Regina B. , Troyanovsky Sergey M.
Published: July 2008

In this work, we show several previously unknown features of p120-catenin in a cadherin–catenin complex that are critical for our understanding of cadherin-based adhesion and signaling. We show that in human epithelial A-431 cells, nearly all p120 molecules engage in high-affinity interaction with E-cadherin–catenin complexes located at the cellular surface. p120 is positioned in proximity to α-catenin in the complex with cadherin. These findings suggest a functional cooperation between p120 and α-catenin in cadherin-based adhesion. A low level of cadherin-free p120 molecules, in contrast, could facilitate p120-dependent signaling. Finally, we present compelling evidence that p120 is a key linker cementing the E-cadherin–catenin complex with the transmembrane protease γ-secretase. The cell–cell contact location of this supercomplex makes it an important candidate for conducting different signals that rely on γ-secretase proteolytic activity.
Antidepressant‐like Effect of l‐perillaldehyde in Stress‐induced Depression‐like Model Mice through Regulation of the Olfactory Nervous System
Authors: Ito N. , Nagai T. , Oikawa T. , Yamada H. , Hanawa T.
Published: July 2008

Perillae Herba (a leaf of Perilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood. l‐Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant‐like effect has not been reported. To clarify the antidepressant‐like effect of PAH, the inhaled effect of PAH on stress‐induced depression‐like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression‐like state was measured by the animal′s duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression‐like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia‐induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant‐like activity through the olfactory nervous function.
Three initial OSPAR tests of ecological coherence: heuristics in a data-limited situation
Authors: Ardron Jeff A.
Published: July 2008

Ardron, J. A. 2008. Three initial OSPAR tests of ecological coherence: heuristics in a data-limited situation. – ICES Journal of Marine Science, 65: 1527–1533. As marine protected area (MPA) networks become established worldwide, it will be necessary to track the progress made in meeting the networks’ underlying ecological goals. The 12 coastal European nations of the OSPAR Convention have agreed to establish an “ecologically coherent” network of MPAs within the waters of the Northeast Atlantic by 2010. However, the meaning of ecological coherence has not been explicitly defined, and it has not been explained how it can be assessed. OSPAR’s work on this topic over the past 4 years is summarized here. As the 2010 deadline approaches, the urgency to assess ecological coherence increases. Proper scientific assessment is hampered by the current lack of detailed ecological data, and policy-makers are concerned that collecting data for indicators will tax already limited resources. Unconventional approaches that can make do with what little information is available are being developed, and three initial spatial tests are presented here. A personal perspective of lessons learnt is provided.
Detection of Adriamycin–DNA adducts by accelerator mass spectrometry at clinically relevant Adriamycin concentrations
Authors: Coldwell Kate E. , Cutts Suzanne M. , Ognibene Ted J. , Henderson Paul T. , Phillips Don R.
Published: July 2008

Limited sensitivity of existing assays has prevented investigation of whether Adriamycin–DNA adducts are involved in the anti-tumour potential of Adriamycin. Previous detection has achieved a sensitivity of a few Adriamycin–DNA adducts/104 bp DNA, but has required the use of supra-clinical drug concentrations. This work sought to measure Adriamycin–DNA adducts at sub-micromolar doses using accelerator mass spectrometry (AMS), a technique with origins in geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay counting) to extract [14C]Adriamycin–DNA adducts from cells and adapted the methodology to AMS detection. Here we show the first direct evidence of Adriamycin–DNA adducts at clinically-relevant Adriamycin concentrations. [14C]Adriamycin treatment (25 nM) resulted in 4.4 ± 1.0 adducts/107 bp (∼1300 adducts/cell) in MCF-7 breast cancer cells, representing the best sensitivity and precision reported to date for the covalent binding of Adriamycin to DNA. The exceedingly sensitive nature of AMS has enabled over three orders of magnitude increased sensitivity of Adriamycin–DNA adduct detection and revealed adduct formation within an hour of drug treatment. This method has been shown to be highly reproducible for the measurement of Adriamycin–DNA adducts in tumour cells in culture and can now be applied to the detection of these adducts in human tissues.
Apparent density patterns in subchondral bone of the sloth and anteater forelimb
Authors: Patel Biren A , Carlson Kristian J
Published: July 2008

Vertebrate morphologists often are interested in inferring limb-loading patterns in animals characterized by different locomotor repertoires. Because bone apparent density (i.e. mass per unit volume of bone inclusive of porosities) is a determinant of compressive strength, and thus indicative of compressive loading, recent comparative studies in primates have proposed a structure–function relationship between apparent density of subchondral bone and locomotor behaviours that vary in compressive loading. If such patterns are found in other mammals, then these relationships would be strengthened further. Here, we examine the distal radius of suspensory sloths that generally load their forelimbs (FLs) in tension and of quadrupedal anteaters that generally load their FLs in compression. Computed tomography osteoabsorptiometry was used to visualize the patterns in subchondral apparent density. Suspensory sloths exhibit relatively smaller areas of high apparent density than quadrupedal anteaters. This locomotor-based pattern is analogous to the pattern observed in suspensory and quadrupedal primates. Similarity between xenarthran and primate trends suggests broad-scale applicability for analysing subchondral bone apparent density and supports the idea that bone functionally alters its material properties in response to locomotor behaviours.
Cell coupling in mouse pancreatic β-cells measured in intact islets of Langerhans
Authors: Zhang Quan , Galvanovskis Juris , Abdulkader Fernando , Partridge Christopher J , Göpel Sven O , Eliasson Lena , Rorsman Patrik
Published: July 2008

The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified β-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent β-cells. Using a combination of current- and voltage-clamp recordings, thetotalgap junctional conductance between β-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell (due to the firing of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of β-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to −55 mV) gave rise to a slow capacitive current indicative of coupling between β-cells, but not in non-β-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial β-cell in an islet is in electrical contact with six to seven other β-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell KATPchannel conductance (GK,ATP) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC50of approximately 4 mM. Theoretical considerations indicate that the coupling between β-cells within the islet is sufficient to allow propagation of [Ca2+]iwaves to spread with a speed of approximately 80 μm s−1, similar to that observed experimentally in confocal [Ca2+]iimaging.
Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice
Authors: Shen Hui-Gang , Zhou Ji-Yong , Huang Zhen-Yu , Guo Jun-Qing , Xing Gang , He Jia-Ling , Yan Yan , Gong Li-Yang
Published: July 2008

The protective immune response against porcine circovirus 2 (PCV2) infection in mice was characterized using flow cytometric analysis (FCM), assays of antibody (of different IgG isotypes) and viraemia, and histopathological examination. An open reading frame 2 plasmid (pORF2) and the capsid protein (Cap) of PCV2 were used as DNA and subunit vaccines, respectively. In FCM analysis, although pORF2 and Cap alone showed comparable efficacy in eliciting lymphoproliferative responses and Cap-specific CD4+ T cells, pORF2 was superior to the Cap protein in triggering CD8+ T cells. A virus neutralization assay showed that pORF2 evoked stronger recall virus-neutralizing (VN) antibody responses than the Cap protein on PCV2 challenge. Correspondingly, VN antibody kinetics coincided with those of Cap-specific IgG2a, but not with the kinetics of IgG and IgG1. Following virus challenge, real-time PCR and histopathological analysis confirmed that only low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized mice. These findings indicate that CD8+ T cells and VN antibody responses correlating mainly with Cap-specific IgG2a play crucial roles in protecting against PCV2 infection, and that the protective immunity induced by the pORF2 plasmid is superior to that induced by the PCV2 Cap protein.
Role of retinoic acid inducible gene-I in human metapneumovirus-induced cellular signalling
Authors: Liao S. , Bao X. , Liu T. , Lai S. , Li K. , Garofalo R. P. , Casola A.
Published: July 2008

Human metapneumovirus (HMPV) is a recently discovered pathogen that causes a significant proportion of respiratory infections in young infants, the elderly and immunocompromised patients. Very little is known regarding the cellular signalling elicited by this virus in airway epithelial cells, the target of HMPV infection. In this study, we investigated the role of the RNA helicases retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene-5 (MDA-5) as the main pattern recognition receptors (PRRs) involved in viral detection and subsequent expression of proinflammatory and antiviral genes. HMPV infection readily induced RIG-I and MDA-5 gene and protein expression in A549 cells, a type II-like alveolar epithelial cell line. Expression of dominant-negative (DN) RIG-I or downregulation of RIG-I gene expression using small interfering RNA (siRNA) significantly decreased HMPV-induced beta interferon (IFN-β), interleukin (IL)-8 and RANTES gene transcription, by inhibiting viral-induced activation of nuclear factor (NF)-κB and interferon regulatory factor (IRF), leading to enhanced viral replication. On the other hand, MDA-5 did not seem to play a significant role in HMPV-induced cellular responses. Mitochondrial antiviral signalling protein (MAVS), an adaptor protein linking both RIG-I and MDA-5 to downstream activation of IRF-3 and NF-κB, was also necessary for HMPV-induced cellular signalling. Expression of a DN MAVS significantly reduced IFN-β and chemokine gene transcription, by inhibiting NF-κB- and IRF-dependent gene transcription, in response to HMPV infection. Our results show that HMPV activates the RIG-I–MAVS signalling pathway in airway epithelial cells, leading to the expression of important proinflammatory and antiviral molecules involved in the innate immune response to viruses.
Identification and characterization of a novel envelope protein in Rana grylio virus
Authors: Zhao Zhe , Ke Fei , Huang You-Hua , Zhao Jiu-Gang , Gui Jian-Fang , Zhang Qi-Ya
Published: July 2008

Viral envelope proteins have been proposed to play significant roles in virus infection and assembly. In this study, an envelope protein gene,53R, was cloned and characterized fromRana gryliovirus (RGV), a member of the familyIridoviridae. Database searches found its homologues in all sequenced iridoviruses, and sequence alignment revealed several conserved structural features shared by virus capsid or envelope proteins: a myristoylation site, two predicted transmembrane domains and two invariant cysteine residues. Subsequently, RT-PCR and Western blot detection revealed that the transcripts encoding RGV 53R and the protein itself appeared late during infection of fathead minnow cells and that their appearance was blocked by viral DNA replication inhibitor, indicating that RGV53Ris a late expression gene. Moreover, immunofluorescence localization found an association of 53R with virus factories in RGV-infected cells, and this association was further confirmed by expressing a 53R–GFP fusion protein in pEGFP-N3/53R-transfected cells. Furthermore, detergent extraction and Western blot detection confirmed that RGV 53R was associated with virion membrane. Therefore, the current data suggest that RGV 53R is a novel viral envelope protein and that it may play an important role in virus assembly. This is thought to be the first report on a viral envelope protein that is conserved in all sequenced iridoviruses.
A comparative cell biological analysis reveals only limited functional homology between the NS5A proteins of hepatitis C virus and GB virus B
Authors: Mankouri Jamel , Milward Andrew , Pryde Kenneth R. , Warter Lucile , Martin Annette , Harris Mark
Published: July 2008

GB virus B (GBV-B) is the closest relative to hepatitis C virus (HCV) with which it shares a common genome organization, however, unlike HCV in humans, it generally causes an acute resolving hepatitis in New World monkeys. It is important to understand the factors regulating the different disease profiles of the two viruses and in this regard, as well as playing a key role in viral RNA replication, the HCV NS5A non-structural protein modulates a variety of host-cell signalling pathways. We have shown previously that HCV NS5A, expressed either alone, or in the context of the complete polyprotein, inhibits the Ras-extracellular-signal-regulated kinase (Erk) pathway and activates the phosphoinositide 3-kinase (PI3K) pathway. In this report, we investigate whether these functions are shared by GBV-B NS5A. Immunofluorescence analysis revealed that a C-terminally FLAG-tagged GBV-B NS5A exhibited a punctate cytoplasmic distribution. However, unlike HCV NS5A, the GBV-B protein did not partially co-localize with early endosomes. Utilizing a transient luciferase reporter system, we observed that GBV-B NS5A failed to inhibit Ras–Erk signalling, however GBV-B NS5A expression did result in the elevation of β-catenin-dependent transcription via activation of the PI3K pathway. These effects of GBV-B and HCV NS5A on the PI3K and Ras–Erk pathways were confirmed in cells harbouring subgenomic replicons derived from the two viruses. Based on these data we speculate that the differential effects of the two NS5A proteins on cellular signalling pathways may contribute to the differences in the natural history of the two viruses.
Restricted Semliki Forest virus replication in perforin and Fas-ligand double-deficient mice
Authors: Alsharifi Mohammed , Lobigs Mario , Bettadapura Jayaram , Koskinen Aulikki , Müllbacher Arno
Published: July 2008

Previously, we have shown that mice defective in granule exocytosis and/or Fas.L/Fas-mediated cytolytic pathways are significantly more resistant to alphavirus, Semliki Forest virus (SFV), infection compared with wild-type mice. Here, we evaluated SFV replication in different tissues of mice defective in both cytolytic pathways (perf−/−xgld) relative to that in wild-type counterparts and found that viral replication in perf−/−xgldmice is remarkably restricted. Although the mechanism responsible for this observation is yet to be established, the lower virus titres found in these mice indicate that the role of cytolytic effector molecules in antiviral immunity needs to be re-evaluated.
The Npro product of classical swine fever virus interacts with IκBα, the NF-κB inhibitor
Authors: Doceul Virginie , Charleston Bryan , Crooke Helen , Reid Elizabeth , Powell Penny P. , Seago Julian
Published: July 2008

Classical swine fever virus(CSFV) belongs to the genusPestivirusand is the causative agent of classical swine fever, a haemorrhagic disease of pigs. The virus replicates in host cells without activating interferon (IFN) production and has been reported to be an antagonist of double-stranded RNA-induced apoptosis. The N-terminal protease (Npro) of CSFV is responsible for this evasion of the host innate immune response. In order to identify cellular proteins that interact with the Nproproduct of CSFV, a yeast two-hybrid screen of a human library was carried out, which identified IκBα, the inhibitor of NF-κB, a transcription factor involved in the control of apoptosis, the immune response and IFN production. The Npro–IκBαinteraction was confirmed using yeast two-hybrid analysis and additional co-precipitation assays. It was also shown that Nprolocalizes to both the cytoplasmic and nuclear compartments in stably transfected cells and in CSFV-infected cells. Following stimulation by tumour necrosis factor alpha, PK-15 cell lines expressing Nproexhibited transient nuclear accumulation of pIκBα, but no effect of CSFV infection on IκBαlocalization or NF-κB p65 activation was observed.
D2: major subgenotype of hepatitis B virus in Russia and the Baltic region
Authors: Tallo Tatjana , Tefanova Valentina , Priimägi Ljudmilla , Schmidt Jelena , Katargina Olga , Michailov Michail , Mukomolov Sergey , Magnius Lars , Norder Heléne
Published: July 2008

Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58–128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtypeayw2, whereas most D2 strains encodedayw3. Two D2 strains encodedayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.
Susceptibility of North American big brown bats (Eptesicus fuscus) to infection with European bat lyssavirus type 1
Authors: Franka R. , Johnson N. , Müller T. , Vos A. , Neubert L. , Freuling C. , Rupprecht C. E. , Fooks A. R.
Published: July 2008

The aim of this study was to determine the susceptibility of insectivorous bats (using the big brown bat as a model) to infection with European bat lyssavirus type 1a (EBLV-1a), to assess the dynamics of host immune responses and to evaluate the opportunity for horizontal viral transmission within colonies. Two isolates of EBLV-1a, originating from Slovakia (EBLV-1aSK) and Germany (EBLV-1aGE), were tested. Four different routes of inoculation were used with isolate EBLV-1aSK [104.8mouse intracerebral median lethal dose (MICLD50) in 50 μl]: intramuscular (i.m.) in the deltoid area or masseter region,per os(p.o.) and intradermal (i.d.) scratches. Isolate EBLV-1aGE (103.2and 102.2MICLD50in 20 μl) was inoculated via the intranasal (i.n.), i.m. (low- and high-dose groups, into pectoral muscles); p.o. and intracerebral (i.c.) routes. None of the bats infected by the i.n., p.o. or i.d. route with either virus isolate developed disease during the experiments (91 or 120 days, respectively). Incubation periods were 9–12 days for i.c.-inoculated bats (66 % mortality), 12–33 days for bats inoculated i.m. with the higher dose (23–50 % mortality) and 21–58 days in bats inoculated i.m. with the lower dose of virus (57 % mortality). Virus or viral RNA in bat saliva was detected occasionally, as early as 37 days before death. All i.d.-inoculated and the majority of i.m.-inoculated bats seroconverted within 7–10 days of inoculation. These observations suggest that exposure of bats to varying doses of EBLV-1 from rabid conspecifics via natural (i.d.) routes could lead to an abortive infection and serve as a natural mode of immunization resulting in the presence of virus-neutralizing antibodies in free-ranging bats.
A Novel ARID DNA-Binding Protein Interacts with SymRK and Is Expressed during Early Nodule Development in Lotus japonicus
Authors: Zhu Hui , Chen Tao , Zhu Maosheng , Fang Qing , Kang Heng , Hong Zonglie , Zhang Zhongming
Published: July 2008

During the establishment of symbiosis in legume roots, the rhizobial Nod factor signal is perceived by the host cells via receptor-like kinases, including SymRK. The NODULE INCEPTION (NIN) gene in Lotus japonicus is required for rhizobial entry into root cells and for nodule organogenesis. We describe here a novel DNA-binding protein from L. japonicus, referred to as SIP1, because it was identified as a SymRK-interacting protein. SIP1 contains a conserved AT-rich interaction domain (ARID) and represents a unique member of the ARID-containing proteins in plants. The C terminus of SIP1 was found to be responsible for its interaction with the kinase domain of SymRK and for homodimerization in the absence of DNA. SIP1 specifically binds to the promoter of LjNIN but not to that of LjCBP1 (a calcium-binding protein gene), both of which are known to be inducible by Nod factors. SIP1 recognizes two of the three AT-rich domains present in the NIN gene promoter. Deletion of one of the AT-rich domains at the NIN promoter diminishes the binding of SIP1 to the NIN promoter. The protein is localized to the nuclei when expressed as a red fluorescence fusion protein in the onion (Allium cepa) epidermal cells. The SIP1 gene is expressed constitutively in the uninfected roots, and its expression levels are elevated after infection by Mesorhizobium loti. It is proposed that SIP1 may be required for the expression of NIN and involved in the initial communications between the rhizobia and the host root cells.
Expression of Umbelopsis ramanniana DGAT2A in Seed Increases Oil in Soybean
Authors: Lardizabal Kathryn , Effertz Roger , Levering Charlene , Mai Jennifer , Pedroso M.C. , Jury Tom , Aasen Eric , Gruys Ken , Bennett Kristen
Published: July 2008

Oilseeds are the main source of lipids used in both food and biofuels. The growing demand for vegetable oil has focused research toward increasing the amount of this valuable component in oilseed crops. Globally, soybean (Glycine max) is one of the most important oilseed crops grown, contributing about 30% of the vegetable oil used for food, feed, and industrial applications. Breeding efforts in soy have shown that multiple loci contribute to the final content of oil and protein stored in seeds. Genetically, the levels of these two storage products appear to be inversely correlated with an increase in oil coming at the expense of protein and vice versa. One way to overcome the linkage between oil and protein is to introduce a transgene that can specifically modulate one pathway without disrupting the other. We describe the first, to our knowledge, transgenic soy crop with increased oil that shows no major impact on protein content or yield. This was achieved by expressing a codon-optimized version of a diacylglycerol acyltransferase 2A from the soil fungus Umbelopsis (formerly Mortierella) ramanniana in soybean seed during development, resulting in an absolute increase in oil of 1.5% (by weight) in the mature seed.
Inorganic structures in space group P3m1; coordinate analysis and systematic prediction of new ferroelectrics
Authors: Abrahams S. C.
Published: July 2008

ICSD Release 2007/1 contains 47 families of inorganic crystal structures, some single-member only, within the 311 entries listed under the polar space group P3m1. Coordinate analysis reveals 12 such families to be candidate ferroelectrics, over a range of confidence levels. Selection is based on the detection of an approach to nonpolar supergroup symmetry, within specified limits, by the atomic arrangement as reported in a confirmed polar space group. The primary source of uncertainty in such predictions is the reliability of the underlying structural determination. The candidates include In2ZnS4, TlSn2F5, Cu7Te4, NaMnSe2, Na2In2(Mo3O8)(MoO4)2, Nb3Br7S, Nb3TeI7, fencooperite, Bi(HCOO)3, Li(NpO2)(CO3)(H2O)2, LiPtD0.66 and Ag3(MoO3F3)(Ag3(MoO4)Cl). A total of 20 structures examined are likely to be nonpolar, a further 20 have reduced predictive properties and three others are more likely to retain P3m1 symmetry over a wide thermal range. Substantial uncertainties associated with many of the listed 163 CdI2, 69 ZnS and 10 SiC polytype structures, together with their low potential for use as possible ferroelectrics, led to their exclusion from fuller analysis.
Hydrogen-bond motifs in the crystals of hydrophobic amino acids
Authors: Fábián László , Chisholm James A. , Galek Peter T. A. , Motherwell W. D. Samuel , Feeder Neil
Published: July 2008

A computer program has been developed to survey a set of crystal structures for hydrogen-bond motifs. Possible ring and chain motifs are generated automatically from a user-defined list of interacting molecular fragments and intermolecular interactions. The new program was used to analyse the hydrogen-bond networks in the crystals of 52 zwitterionic α-amino acids. All the possible chain motifs (repeating 1–4 molecules) are frequent, while the frequency of ring motifs (2–6 molecules) ranges from 0 to 85% of the structures. The list of motifs displayed by each structure reveals structural similarities and it can be used to compare polymorphs. The motifs formed in cocrystals of α-amino acids and in crystals of β- and γ-amino acids are similar to those of α-amino acids.
Browsing impact of large herbivores on Acacia xanthophloea Benth in Lake Nakuru National Park, Kenya
Authors: Dharani N. , Kinyamario J. I. , Wagacha Peter W. , Rodrigues Anthony J.
Published: July 2008

Significant differences (P<0.05) were found in growth of plant height, canopy cover and stem diameter of Acacia xanthophloea trees in fenced plot as compared with unfenced plot both in the wet and in the dry seasons. Finding of this study showed that although heavy browsing reduced the height and canopy of trees, it did not kill any trees and seedling regeneration took place simultaneously. Despite the presence of large herbivores that impact some considerable browsing pressure results indicate that the A. xanthophloea habitat type would continue to remain in balance in the presence of recruitment of seedlings and saplings. The conditions at the time of study indicate that the browsing on A. xanthophloea was not significant and was not serious enough to warrant management intervention at present.
Systematic review of the literature for the use of oesophageal Doppler monitor for fluid replacement in major abdominal surgery
Authors: Abbas S. M. , Hill A. G.
Published: July 2008

The use of intra‐operative Doppler oesophageal probes provides continuous monitoring of cardiac output. This enables optimisation of intravascular volume and tissue perfusion in major abdominal surgery, which is thought to reduce postoperative complications and shorten hospital stay. Medline and EMBASE were searched using the standard methodology of the Cochrane collaboration for trials that compared oesophageal Doppler monitoring with conventional clinical parameters for fluid replacement in patients undergoing major elective abdominal surgery. Data from randomised controlled trials were entered and analysed in Meta‐view in Rev‐Man 4.2 (Nordic, Denmark). We included five studies that recruited 420 patients undergoing major abdominal surgery who were randomly allocated to receive either intravenous fluid treatment guided by monitoring ventricular filling using oesophageal Doppler monitor or fluid administration according to conventional parameters. Pooled analysis showed a reduced hospital stay in the intervention group. Overall, there were fewer complications and ICU admissions, and less requirement for inotropes in the intervention group. Return of normal gastro‐intestinal function was also significantly faster in the intervention group. Oesophageal Doppler use for monitoring and optimisation of flow‐related haemodynamic variables improves short‐term outcome in patients undergoing major abdominal surgery.
Phaeochromocytoma crisis – a rare indication for extracorporeal membrane oxygenation
Authors: Chao A. , Yeh Y. C. , Yen T. S. , Chen Y. S.
Published: July 2008

We report on a case of phaeochromocytoma whose initial presentation mimicked an acute myocardial infarction. Veno‐arterial extracorporeal membrane oxygenation was used for the management of refractory cardiogenic shock and massive lung oedema. Suspicion and diagnosis of a phaeochromocytoma were made due to its unique clinical presentation during extracorporeal membrane oxygenation. Stabilisation of the crisis and recovery of cardiopulmonary function were achieved using the support of extracorporeal membrane oxygenation. This case highlights the difficulty in the differential diagnosis of cardiogenic shock secondary to phaeochromocytoma and the important role of extracorporeal membrane oxygenation can have in the successful resuscitation and management of these patients.
Airtraq vs standard laryngoscopy by student paramedics and experienced prehospital laryngoscopists managing a model of difficult intubation*
Authors: Woollard M. , Lighton D. , Mannion W. , Watt J. , McCrea C. , Johns I. , Hamilton L. , O'Meara P. , Cotton C. , Smyth M.
Published: July 2008

Two consecutive, randomised, cross‐over trials compared intubation success rates in third‐year paramedic students and experienced prehospital practitioners using the Airtraq or a Macintosh laryngoscope with flexible stylet in a manikin model of a Cormack and Lehane grade III/IV laryngoscopic view. First‐time intubation rates for the Macintosh and Airtraq for students were 0/23 (0%) vs 10/23 (44%) (44% difference, 95% CI 26–63%, p < 0.001) and for experienced laryngoscopists were 14/56 (25%) vs 47/56 (84%) (59% difference, 95% CI 42–72%, p < 0.0001), respectively. First‐time oesophageal intubation rates for students were 15/23 (65%) vs 3/23 (13%) (− 52% difference, 95% CI − 25 to − 72%, p < 0.001) and for experienced practitioners 9/56 (16%) vs 0/56 (0%) (− 16% difference, 95% CI − 9 to − 28%, p = 0.0014). Student paramedics and experienced prehospital laryngoscopists managing a manikin model of a grade III/IV view had increased first‐time intubation rates and had lower rates of oesophageal intubation with the Airtraq compared with a standard laryngoscope.
The effect of flow on the filtration performance of paediatric breathing system filters
Authors: Wilkes A. R. , Malan C. A. , Hall J. E.
Published: July 2008

The effect of flow on the filtration performance of six different types of filter intended for use in paediatric anaesthesia was measured by challenging the filters with sodium chloride particles at five different flows: 6, 10, 15, 20 and 30 l.min−1. Twenty‐five unused samples of each filter type were evaluated. The pressure drop across each filter was measured at the same flows as those used to measure penetration. The pressure drop varied both between and within the types of filter. Mean pressure drop varied between 89 and 262 Pa at a flow of 15 l.min−1 for the six different filters. Penetration of sodium chloride particles varied from 1.9 to 18% at 15 l.min−1 for the six filters. Allowing for the variation in pressure drop, the penetration of particles increased fairly linearly as flow increased for all six filter types. The increase in penetration per unit increase in flow varied from 0.11 to 0.82% per litre per minute. Over the range of flows studied, the increase in penetration with flow is fairly predictable.
The effect of volatile anaesthetic agents on the filtration performance of paediatric breathing system filters*
Authors: Froom S. R. , Cann C. , Wilkes A. R. , Gildersleve C. , Hall J. E.
Published: July 2008

The aim of this study was to determine the filtration performance of five commonly used paediatric breathing system filters following exposure to desflurane, isoflurane and sevoflurane. It has been suggested that oil may degrade the performance of filter material. Volatile anaesthetic vapours are organic and hence may affect the filtration performance of breathing system filters during anaesthesia. This has not been tested for various concentrations of volatile agent, type and duration of exposure. The filtration performance of the filters was measured following exposure to desflurane, isoflurane and sevoflurane at 1 and 2 minimum alveolar concentration (MAC) for 1 and 4 h. Penetration of particles through the Clear‐Therm Micro, Clear‐Therm Mini and Humid‐Vent Filter Pedi increased by between 2.4 and 2.8 times after exposure to desflurane at 2 MAC for 4 h compared to that through unexposed filters (p < 0.0001 for all three filters). Further investigation is required to determine whether this reduction in filtration performance by desflurane is clinically significant.
Randomised crossover comparison of the Ambu® AuraOnceTM Laryngeal Mask with the LMA ClassicTM laryngeal mask airway in paralysed anaesthetised patients*
Authors: Shariffuddin I. I. , Wang C. Y.
Published: July 2008

We compared the performance of the Ambu® AuraOnceTM Laryngeal Mask with that of the LMA ClassicTM laryngeal mask airway during controlled anaesthesia. Forty patients requiring intermittent positive pressure ventilation were studied using a randomised crossover design. The mean (SD) oropharyngeal leak pressure for the Ambu device (19 (7.5) cmH2O) was significantly greater than for the LMA Classic (15 (5.2) cmH2O; p = 0.004), and the number of attempts for successful insertions was significantly less (39 (50%) vs 45 (56%), respectively; p = 0.02). There was one failure to obtain a patent airway with the Ambu Laryngeal Mask and none with the LMA Classic. Insertion of the Ambu Laryngeal Mask required more manipulations to achieve a patent airway than did the LMA Classic (6 (15%) vs 1 (2.5%), respectively; p = 0.045), but the time taken for insertion was similar between the two groups. The incidence of trauma, grade of fibreoptic view, peak airway pressure and quality of ventilation during maintenance of anaesthesia were similar in both groups.
Accidental dural puncture and post dural puncture headache in obstetric anaesthesia: presentation and management: A 23‐year survey in a district general hospital
Authors: Sprigge J. S. , Harper S. J.
Published: July 2008

Post dural puncture headache can be a debilitating complication of epidural and subarachnoid anaesthesia for a new mother. In a survey of 18 337 epidurals and 5021 subarachnoid blocks performed for obstetric procedures over a 23‐year period in a district general hospital maternity unit, there were 167 recognised accidental dural punctures after epidurals (0.91%), with 147 patients (88%) developing post dural puncture headache. In addition there were 52 post dural puncture headaches after subarachnoid blocks (1.04%). Successful management of accidental dural puncture and post dural puncture headache requires adherence to clear policies and protocols, with close follow‐up of patients by an experienced obstetric anaesthetist.
Assessment of manoeuvres required for successful blind tracheal intubation through the PAXpress™
Authors: Ahmed S. M. , Khan R. M. , Maroof M. , Ahmed M.
Published: July 2008

A PAXpress™ (Vital Signs Inc., Barnham, UK) airway device was placed in 50 adult ASA grade I and II patients undergoing elective surgery under general anaesthesia. The alignment of the PAXpress to the larynx was scored fibreoptically. The patients were then intubated blindly through the PAXpress and the adjusting manoeuvres required for successful intubation and complications of intubation observed. Insertion of the PAXpress was successful in all patients, and intubation was successful in 42 (84%) patients. Eleven patients were intubated in the neutral position, seven with a flexion manoeuvre and 24 with an extension manoeuvre. Intubation was successful in 17/20, 18/20, 6/8 and 1/2 of patients with a fibreoptic alignment score of 1, 2, 3 and 4, respectively. When the fibreoptic alignment score was between 2 and 4 intubation was achieved predominantly with the extension manoeuvre (20/30, 66%) rather than the flexion manoeuvre (1/30, 3%) or the neutral position (5/30, 16%). Blood staining was observed in 20 patients. We conclude that blind tracheal intubation through PAXpress has a moderately good success rate and a high incidence of mucosal trauma. ‘Extension’ is the predominant adjusting manoeuvre required for blind tracheal intubation, especially when the alignment of the PAXpress to the larynx is poor.
Calcitriol blunts pro‐atherosclerotic parameters through NFκB and p38 in vitro
Authors: Talmor Y. , Bernheim J. , Klein O. , Green J. , Rashid G.
Published: July 2008

Background  Disturbances in vitamin D3 metabolism are associated with an increased cardiovascular morbidity and mortality. The aim of this study was to assess the effects of calcitriol, the active metabolite of vitamin D3, on pro‐atherosclerotic parameters in human umbilical vein cord endothelial cells (HUVEC).

Materials and methods  Calcitriol at 10−10 and/or 10−9 mol L−1 was given to cultured HUVEC which were either non‐stimulated or lipopolysaccharide (LPS) stimulated. Inter cellular adhesion molecule‐1 and platelet‐endothelial cell adhesion molecule‐1, were determined by flow cytometry analysis. The receptor of advanced glycation end product (RAGE) and interleukin‐6 (IL‐6) mRNA expressions by RT‐PCR and IL‐6 secretion by enzyme‐linked immunosorbent assay (ELISA). Nuclear p65 DNA‐binding activity was measured by transcription factor assay kit and the inhibitor‐κBα (IκBα), phosphorylated‐IκBα (P‐IκBα) and phosphorylated‐p38 mitogen‐activated protein kinase (MAPK) protein levels were determined by Western blot.

Results  Calcitriol decreased the adhesion molecules expression, as well as the LPS‐induced mRNA expressions of RAGE and IL‐6 and LPS induced IL‐6 secretion. Furthermore, the LPS induced nuclear factor κB (NFκB)‐p65 DNA‐binding activity was also decreased by calcitriol. IκBα levels were increased and p‐IκBα levels decreased after calcitriol treatment. The increased levels of activated p38 MAPK after LPS treatment were also decreased due to pre‐incubation with calcitriol.

Conclusions  The decreased NFκB and p38 activities followed by calcitriol treatment may explain the anti‐inflammatory/atherosclerotic properties of calcitriol that were observed previously and were emphasized in this study, demonstrating the inhibitory effect of calcitriol on the pro‐inflammatory parameters: adhesion molecules, RAGE and IL‐6.
Cardiac and kidney hormones cure up to 86% of human small‐cell lung cancers in mice
Authors: Eichelbaum E.J. , Sun Y. , Alli A.A. , Gower W.R. , Vesely D.L.
Published: July 2008

Background  Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, and the kidney hormone urodilatin have anticancer effects in vitro.

Materials and Methods  These cardiac hormones and urodilatin were infused subcutaneously for 28 days with weekly fresh hormones since they lose biological effects at body temperature for more than a week at 0·3 nm kg−1 body weight in athymic mice bearing human small‐cell lung carcinomas.

Results  Long acting natriuretic peptide, vessel dilator, kaliuretic peptide, atrial natriuretic peptide and urodilatin eliminated 86%, 71%, 57%, 43% (P < 0·001 for the cardiac hormones) and 25% (P < 0·05; urodilatin) of the human small‐cell lung carcinomas. The treated small‐cell lung carcinomas that were not cured grew rapidly, similar to the untreated controls, whose volume was 7 fold larger in 1 week, 18‐fold increased in 2 weeks, 39‐fold increased in 3 weeks, 63‐fold increased in 1 month and 97‐fold increased in volume in 6 weeks. One vessel dilator treated small‐cell lung carcinoma animal developed a large tumour (8428 mm3 volume) on treatment and this tumour was eliminated with utilizing atrial natriuretic peptide and then long acting natriuretic peptide sequentially.

Conclusions  Four cardiac hormones eliminate up to 86% of human small‐cell lung carcinomas in athymic mice. Urodilatin can also eliminate small‐cell lung carcinomas but at a lower cure rate of 25%. Unresponsive lesions can be eliminated by utilizing different hormones synthesized by the atrial natriuretic peptide gene in a sequential manner.