bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying leaf venation patterns: two‐dimensional maps
Authors: Rolland‐Lagan Anne‐Gaëlle , Amin Mira , Pakulska Malgosia
Published: September 2008

The leaf vasculature plays crucial roles in transport and mechanical support. Understanding how vein patterns develop and what underlies pattern variation between species has many implications from both physiological and evolutionary perspectives. We developed a method for extracting spatial vein pattern data from leaf images, such as vein densities and also the sizes and shapes of the vein reticulations. We used this method to quantify leaf venation patterns of the first rosette leaf of Arabidopsis thaliana throughout a series of developmental stages. In particular, we characterized the size and shape of vein network areoles (loops), which enlarge and are split by new veins as a leaf develops. Pattern parameters varied in time and space. In particular, we observed a distal to proximal gradient in loop shape (length/width ratio) which varied over time, and a margin‐to‐center gradient in loop sizes. Quantitative analyses of vein patterns at the tissue level provide a two‐way link between theoretical models of patterning and molecular experimental work to further explore patterning mechanisms during development. Such analyses could also be used to investigate the effect of environmental factors on vein patterns, or to compare venation patterns from different species for evolutionary studies. The method also provides a framework for gathering and overlaying two‐dimensional maps of point, line and surface morphological data.
General trait relationships in stems: a study on the performance and interrelationships of several functional and structural parameters involved in corticular photosynthesis
Authors: Wittmann Christiane , Pfanz Hardy
Published: September 2008

We addressed corticular photosynthesis, focusing on parameters of underlying dark and light reactions as well as structural differentiation. To unveil general stem traits and underlying principles that may be valid across several tree species, CO2 exchange rates and chlorophyll‐fluorescence parameters were measured in current‐year to 3‐year‐old stems of five deciduous tree species (including climax and pioneer species). Across species, dark CO2 efflux rates (Rd) of stems exhibited a common regression relationship with photosynthetic rates (A) and light‐adapted quantum efficiency of photosystem II (PSII) (ΔF/Fm′), a pattern analogous to leaf trait correlations. Furthermore, A and ΔF/Fm′ were closely interrelated to each other. Consistent correlations of stem structure and function were also assessed among species. Changes in tissue structure during ageing significantly affected several stem functional parameters. Stem CO2 efflux during the dark and corticular photosynthetic rates declined with increasing stem age as well as light‐adapted quantum efficiency of PSII. Furthermore, a strong relationship between stem Rd and peridermal PFD‐transmittance (T) as well as between Rd and total bark chlorophyll was evident. Consistent results were found for the relationships between corticular photosynthesis (or primary photosynthetic reactions like ΔF/Fm′) and selected structural traits. The found correlation patterns among functional and/or structural traits of stems and their concordance with leaf trait relationships may aid in identifying underlying mechanisms and scaling relationships that link traits to plant and ecosystem function.
Light and temperature regulation of greening in dark‐grown ginkgo (Ginkgo biloba)
Authors: Skribanek Anna , Solymosi Katalin , Hideg Éva , Böddi Béla
Published: September 2008

The last steps of chlorophyll (Chl) biosynthesis were studied at different light intensities and temperatures in dark‐germinated ginkgo (Ginkgo biloba L.) seedlings. Pigment contents and 77 K fluorescence emission spectra were measured and the plastid ultrastructure was analysed. All dark‐grown organs contained protochlorophyllide (Pchlide) forms with similar spectral properties to those of dark‐grown angiosperm seedlings, but the ratios of these forms to each other were different. The short‐wavelength, monomeric Pchlide forms were always dominating. Etioplasts with small prolamellar bodies (PLBs) and few prothylakoids (PTs) differentiated in the dark‐grown stems. Upon illumination with high light intensities (800 μmol m−2 s−1 photon flux density, PFD), photo‐oxidation and bleaching occurred in the stems and the presence of 1O2 was detected. When Chl accumulated in plants illuminated with 15 μmol m−2 s−1 PFD it was significantly slower at 10°C than at 20°C. At room temperature, the transformation of etioplasts into young chloroplasts was observed at low light, while it was delayed at 10°C. Grana did not appear in the plastids even after 48 h of greening at 20°C. Reaccumulation of Pchlide forms and re‐formation of PLBs occurred when etiolated samples were illuminated with 200 μmol m−2 s−1 PFD at room temperature for 24 h and were then re‐etiolated for 5 days. The Pchlide forms appeared during re‐etiolation had similar spectral properties to those of etiolated seedlings. These results show that ginkgo seedlings are very sensitive to temperature and light conditions during their greening, a fact that should be considered for ginkgo cultivation.
Chloroplastic glutamine synthetase is activated by direct binding of aluminium
Authors: Pécsváradi Attila , Nagy Zoltán , Varga Anikó , Vashegyi Ágnes , Labádi Imre , Galbács Gábor , Zsoldos Ferenc
Published: September 2008

Acidification of soils may release water soluble, toxic aluminium species from clay minerals. Al interferes with a wide range of physical and cellular processes. Glutamine synthetase (GS, EC 6.3.1.2) is the key enzyme of primary N assimilation, as well as ammonia reassimilation and detoxification. Plant GS requires two magnesium ions per subunit for activity, which makes GS a potential target of metal stress. The objective of this investigation was to prove that Al from an organic metal complex is able to activate GS, and Al becomes bound to the polypeptide structure of the GS molecule. Aluminium(III)–nitrilotriacetic acid complex (Al(III)NTA) activated the GS prepared from wheat (Triticum aestivum L.) leaves, as Al3+ did in vivo, but could not functionally substitute magnesium ions, which were also necessary for the activity in the in vitro GS assay. GS2 was isolated by non‐denaturing polyacrylamide gel electrophoresis, and the Al and Mg content of the enzyme was determined by inductively coupled plasma atomic emission spectroscopy. The GS octamer remained intact and contained Mg2+ bound to its specific sites after the electrophoretic separation. Al was detected in the Al(III)NTA‐treated sample bound to the structure of the enzyme protein, potentially occupying one of the specific metal‐binding sites of the subunits. Our results indicate that the activatory effect of the Al(III)NTA complex is because of specific binding of aluminium to the polypeptide chain of GS2, however presence of magnesium at least on one of the metal‐binding sites is essential to the active state of the enzyme.
Relative contribution of AtHAK5 and AtAKT1 to K+ uptake in the high‐affinity range of concentrations
Authors: Rubio Francisco , Nieves‐Cordones Manuel , Alemán Fernando , Martínez Vicente
Published: September 2008

The relative contribution of the high‐affinity K+ transporter AtHAK5 and the inward rectifier K+ channel AtAKT1 to K+ uptake in the high‐affinity range of concentrations was studied in Arabidopsis thaliana ecotype Columbia (Col‐0). The results obtained with wild‐type lines, with T‐DNA insertion in both genes and specific uptake inhibitors, show that AtHAK5 and AtAKT1 mediate the ‐sensitive and the Ba2+‐sensitive components of uptake, respectively, and that they are the two major contributors to uptake in the high‐affinity range of Rb+ concentrations. Using Rb+ as a K+ analogue, it was shown that AtHAK5 mediates absorption at lower Rb+ concentrations than AtAKT1 and depletes external Rb+ to values around 1 μM. Factors such as the presence of K+ or during plant growth determine the relative contribution of each system. The presence of in the growth solution inhibits the induction of AtHAK5 by K+ starvation. In K+‐starved plants grown without , both systems are operative, but when is present in the growth solution, AtAKT1 is probably the only system mediating Rb+ absorption, and the capacity of the roots to deplete Rb+ is reduced.
Stigmatisation in onychomycosis patients: a population‐based study
Authors: Szepietowski Jacek C. , Reich Adam ,   for the National Quality of Life in Dermatology Group
Published: September 2008

Patients with onychomycosis may experience significant psychosocial problems, similarly to other skin diseases. The objectives of this study were to analyse the level of stigmatisation among subjects with onychomycosis and the effect of anti‐mycotic therapy on this feeling. This prospective study was carried out among 1684 patients (1050 women and 634 men, mean age 52.2 ± 15.5 years) with onychomycosis. All subjects were asked to fulfil the stigmatisation questionnaire at the baseline visit and after the completion of the anti‐mycotic therapy. Stigmatisation level was assessed with reference to gender, age, education, type and duration of onychomycosis and the number of involved nails. Patients with onychomycosis reported markedly increased feeling of stigmatisation. Fingernail involvement was the major variable negatively influencing the stigmatisation level. Female patients and younger ones appeared to be more stigmatised. No significant relationships were found between stigmatisation level and education, number of involved fingernails or toenails, as well as the duration of onychomycosis. The anti‐mycotic therapy resulted in significant reduction of all analysed aspects of stigmatisation to about 40% of the baseline level. Onychomycosis should be considered as an important problem for patients, significantly reducing their physical, mental and social well‐being, also leading to marked stigmatisation of patients.
Association of Vibrio cholerae with plankton in coastal areas of Mexico
Authors: Lizárraga‐Partida M. L. , Mendez‐Gómez E. , Rivas‐Montaño A. M. , Vargas‐Hernández E. , Portillo‐López A. , González‐Ramírez A. R. , Huq A. , Colwell R. R.
Published: September 2008

The El Niño event of 1997/1998 provided an opportunity to carry out a field experiment in which the relationship of sea surface temperature and the association of Vibrio cholerae with marine plankton could be assessed in Mexican coastal and estuarine areas. Plankton samples were collected from May 1997 through June 1999. Sites included the Mexican ports of Veracruz, Coatzacoalcos and Frontera in the Gulf of Mexico and Ensenada, Guaymas, Mazatlán, Manzanillo, Acapulco and Oaxaca in the Pacific Ocean. Sampling was also accomplished during two oceanographic cruises in the Yucatan channel of the Caribbean Sea. Bacteriological analyses for V. cholerae serogroups O1 and O139 were carried out. Also, the taxonomic structure of the plankton populations was determined. Vibrio cholerae O1 was detected only in Veracruz samples collected during April, May and June 1999, when La Niña climatic conditions prevailed. It is concluded that V. cholerae O1 in Mexico derives from its marine and estuarine origin and not from sewage contamination. The significant number of Acartia tonsa copepodites and V. cholerae copepodite‐positive samples suggests a significant role of this copepod in the occurrence and distribution of V. cholerae in coastal areas of Mexico.
13C‐isotope analyses reveal that chemolithoautotrophicGamma‐ andEpsilonproteobacteriafeed a microbial food web in a pelagic redoxcline of the central Baltic Sea
Authors: Glaubitz Sabine , Lueders Tillmann , Abraham Wolf‐Rainer , Jost Günter , Jürgens Klaus , Labrenz Matthias
Published: September 2008

Marine pelagic redoxclines are zones of high dark CO2fixation rates, which can correspond up to 30% of the surface primary production. However, despite this significant contribution to the pelagic carbon cycle, the identity of most chemolithoautotrophic organisms is still unknown. Therefore, the aim of this study was to directly link the dark CO2fixation capacity of a pelagic redoxcline in the central Baltic Sea (Landsort Deep) with the identity of the main chemolithoautotrophs involved. Our approach was based on the analysis of natural carbon isotope signatures in fatty acid methyl esters (FAMEs) and on measurements of CO2incorporation in13C‐bicarbonate pulse experiments. The incorporation of13C into chemolithoautotrophic cells was investigated by rRNA‐based stable isotope probing (RNA‐SIP) and FAME analysis after incubation for 24 and 72 h underin situconditions. Our results demonstrated that fatty acids indicative ofProteobacteriawere significantly enriched in13C slightly below the chemocline. RNA‐SIP analyses revealed that two differentGammaproteobacteriaand three closely relatedEpsilonproteobacteriaof theSulfurimonascluster were active dark CO2‐fixing microorganisms, with a time‐dependent community shift between these groups. Labelling ofArchaeawas not detectable, but after 72 h of incubation the13C‐label had been transferred to a potentially bacterivorous ciliate related toEuplotessp. Thus, RNA‐SIP provided direct evidence for the contribution of chemolithoautotrophic production to the microbial food web in this marine pelagic redoxcline, emphasizing the importance of dark CO2‐fixingProteobacteriawithin this habitat.
Life‐course socio‐economic position, area deprivation and Type 2 diabetes: findings from the British Women's Heart and Health Study
Authors: Andersen A. F. , Carson C. , Watt H. C. , Lawlor D. A. , Avlund K. , Ebrahim S.
Published: September 2008

Objectives  We examined whether area deprivation influenced risk of Type 2 diabetes, fasting blood glucose and insulin resistance over and above the effect of individual socio‐economic position (SEP) measured across the life course.

Methods  A cross‐sectional analysis of 4286 women aged 60 to 79 years from 457 British electoral wards in 23 towns.

Results  Area deprivation was positively associated with diagnosed [odds ratio (OR) 1.32, 95% confidence interval (CI) 1.13, 1.53, per quintile of area deprivation, n = 2895], but not undiagnosed Type 2 diabetes after adjustment for individual life‐course SEP. This association was robust to adjustment for adult health behaviours and physiological risk factors. Insulin resistance [homeostasis model assessment (HOMA) score] increased by 1.90% (95% CI 0.01, 3.82, n = 2526) per quintile of area deprivation after adjustment for individual SEP, while fasting blood glucose increased by 0.69% (95% CI 0.16, 1.22, n = 2875) after adjustment for individual SEP.

Conclusions  Area level deprivation independently influences diagnosed Type 2 diabetes, insulin resistance and fasting blood glucose. Examination of more specific characteristics of places is needed to understand the mechanisms by which these effects arise.
A Ranking of Journals in Economics and Related Fields
Authors: Ritzberger Klaus
Published: September 2008

This paper presents an update of the ranking of economics journals by the invariant method, as introduced by Palacio-Huerta and Volij, with a broader sample of journals. By comparison with the two other most prominent rankings, it also proposes a list of ‘target journals’, ranked according to their quality, as a standard for the field of economics.
Research Productivity in Business Economics: An Investigation of Austrian, German and Swiss Universities
Authors: Fabel Oliver , Hein Miriam , Hofmeister Robert
Published: September 2008

We draw on a new and comprehensive dataset that collects the research output of business economists employed by Austrian, German and Swiss universities. We compute research rankings of departments and identify the leading departments in selected subdisciplines. Moreover, we investigate how institutional design and individual characteristics affect research productivity and draw some conclusions for the training of junior scientists.
The impact of climate change on long‐term population trends of birds in a central European country
Authors: Reif J. , Voříšek P. , Št'astný K. , Koschová M. , Bejček V.
Published: September 2008

Numerous studies have shown that climate changes associated with increasing global temperature affect bird species. For instance, long‐distance migrants are not able to respond adequately to rapid advances in spring phenology, and thus their populations decline due to lower breeding performance. Moreover, many species in the Northern Hemisphere have shifted their northern breeding range boundaries further north. However, studies focusing on bird populations at the scale of individual countries, which are responsible for creating environmental policies, are rather scarce. We hypothesized that bird species with different European latitudinal breeding distributions would have different long‐term population trends in the Czech Republic, a small central European country, as a result of range dynamics caused by increasing spring temperature. In accordance with this prediction, the results of an analysis based on large‐scale monitoring data (from 1982 to 2006) showed that species with more northern latitudinal distributions had more negative population trends in the Czech Republic. However, the strength of the relationship depended on the approach used for characterization of the species latitudinal distributions. When a phylogenetic regression was applied, the only significant explanatory variable was the latitudinal distribution expressed in categories defined by species range areas in different latitudinal bands. A more detailed analysis showed that southern and northern species groups have opposite population trajectories: the former increased and the latter declined throughout the study period. The effect of climate change remained significant when habitat association and the migratory strategy of each species were taken into account. However, it is difficult to determine whether climate change or habitat change is the more important driver of long‐term trends in bird populations as the effects of both factors are dependent on interspecific variability in levels of species specialization.
Regulation of the pH sensitivity of human P2X3 receptors by N‐linked glycosylation
Authors: Wirkner Kerstin , Stanchev Doychin , Milius Doreen , Hartmann Lars , Kato Erzsebet , Zadori Zoltan S. , Mager Peter P. , Rubini Patrizia , Nörenberg Wolfgang , Illes Peter
Published: September 2008

The human (h) P2X3 receptor and its mutants deficient in one out of four N‐glycosylation sites were expressed in HEK293 cells. Concentration–response curves were generated by whole‐cell recordings of α,β‐methylene ATP (α,β‐meATP)‐induced currents. A gradual change of external pH from the alkaline 8.0 to the acidic 5.0 successively decreased the maximum current amplitude (Emax) without affecting the EC50 value. The replacement of Asn‐139 and ‐170 by Asp (N139D, N170D) abolished the pH sensitivity of the wild‐type (WT) hP2X3 receptor. In the case of N194D, the Emax was again the highest at the alkaline pH value with no change from 7.4 to 6.5, whereas in the case of N290D, there was an inverse pH sensitivity, with an increase of Emax in the acidic range. However, this effect appeared to be due to enhanced protonation by the insertion of Asp into the receptor, because replacement of Asn by the neutral Thr resulted in a comparable potency of α,β‐meATP at any of the pH values investigated. In accordance with the reported finding that His‐206 is involved in the modulation of WT P2X3 receptors by protons, we showed that the normal change of Emax by an acidic, but not alkaline pH was abolished after substitution of this His by Ala. However, the double mutant H206A + N290D did not react to acidification or alkalinization with any change in Emax. In conclusion, only fully N‐glycosylated P2X3 receptors recognize external pH with a modified sensitivity towards α,β‐meATP.
Inhibition of rat glioma cell migration and proliferation by a calix[8]arene scaffold exposing multiple GlcNAc and ureido functionalities
Authors: Viola Santa , Consoli Grazia M. L. , Merlo Sara , Drago Filippo , Sortino Maria Angela , Geraci Corrada
Published: September 2008

β1,4‐Galactosyltransferases (β1,4‐GalTase) exposed on the cell surface are involved in cell migration. Specifically, β1,4‐GalTase V is highly expressed in glioma and promotes invasion, growth, and survival of glioma cells. A glycocalix[8]arene exposing N‐acetylglucosamine (GlcNAc) residues (compound 1) inhibited rat C6 glioma cell migration as assessed in a scratch wound model. This effect was related to inhibition of focal adhesion kinase phosphorylation, measured by western blot analysis, and specifically observed in the area bordering the scratch wound. Compound 1 inhibited also C6 cell proliferation, an effect unrelated to its ability to interact with GalTase as it was mimicked by different calix[8]arene derivatives, all characterized by multivalency and ureido groups. Compound 1 did not induce apoptotic death, but caused a different distribution of C6 cells within the cell cycle. The results here reported identify compound 1 as a molecule able to exert inhibitory effects on C6 cell migration and proliferation, independently, because of distinct components in its structure.
Mitogen‐activated protein kinase activity may not be necessary for the neuropathology of Niemann–Pick type C mice
Authors: Zhang Min , Hallows Janice L. , Wang Xuezhen , Bu Bitao , Wang Wei , Vincent Inez
Published: September 2008

Hyperphosphorylation of neurofilament and tau, and formation of cytoskeletal lesions, are notable features of several human neurodegenerative diseases, including Niemann‐Pick Disease Type C (NPC). Previous studies suggested that the MAPKs, extracellular signal regulated kinase 1 and 2 (ERK1/2) may play a significant role in this aspect of NPC. To test this idea, we treated npc mice with PD98059, a specific and potent inhibitor of MAPK activation. Although activity of ERK1/2 was inhibited by 40%, a 2‐week intracerebroventricular infusion of PD98059 just prior to onset of cytoskeletal pathology and symptoms in npc mice did not delay or inhibit prominent hallmarks of NPC. Unexpectedly, ERK1/2 inhibition led to aggravation of tau hyperphosphorylation, particularly in oligodendroctyes, in a manner similar to that of certain human tauopathies. Our results suggest that ERK1/2 does not play a major role in NPC neuropathology, and therefore, that MAPK inhibition is unlikely to be a useful strategy for managing the disease.
Protease‐activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines
Authors: Vandell Alexander G. , Larson Nadya , Laxmikanthan Gurunathan , Panos Michael , Blaber Sachiko I. , Blaber Michael , Scarisbrick Isobel A.
Published: September 2008

While protease‐activated receptors (PARs) are known to mediate signaling events in CNS, contributing both to normal function and pathogenesis, the endogenous activators of CNS PARs are poorly characterized. In this study, we test the hypothesis that kallikreins (KLKs) represent an important pool of endogenous activators of CNS PARs. Specifically, KLK1 and KLK6 were examined for their ability to evoke intracellular Ca2+ flux in a PAR‐dependent fashion in NSC34 neurons and Neu7 astrocytes. Both KLKs were also examined for their ability to activate mitogen‐activated protein kinases (extracellular signal‐regulated kinases, C‐Jun N‐terminal kinases, and p38) and protein kinase B (AKT) intracellular signaling cascades. Cumulatively, these studies show that KLK6, but not KLK1, signals through PARs. KLK6 evoked intracellular Ca2+ flux was mediated by PAR1 in neurons and both PAR1 and PAR2 in astrocytes. Importantly, both KLK1 and KLK6 altered the activation state of mitogen‐activated protein kinases and AKT, suggestive of important roles for each in CNS neuron and glial differentiation, and survival. The cellular specificity of CNS–KLK activity was underscored by observations that both proteases promoted AKT activation in astrocytes, but inhibited such signaling in neurons. PAR1 and bradykinin receptor inhibitors were used to demonstrate that KLK1‐mediated activation of extracellular signal‐regulated kinases in neurons occurred in a non‐PAR, bradykinin 2 (B2) receptor‐dependent fashion, while similar signaling by KLK6 was mediated by the combined activation of PAR1 and B2. Cumulatively results indicate KLK6, but not KLK1 is an activator of CNS PARs, and that both KLKs are poised to signal in a B2 receptor‐dependent fashion to regulate multiple signal transduction pathways relevant to CNS physiologic function and dysfunction.
Mechanisms for recycling and biosynthesis of endogenous cannabinoids anandamide and 2‐arachidonylglycerol
Authors: Placzek Ekaterina A. , Okamoto Yasuo , Ueda Natsuo , Barker Eric L.
Published: September 2008

The mechanisms of endogenous cannabinoid biosynthesis are not completely understood. We hypothesized that anandamide could be recycled by the cell to form new endocannabinoid molecules and released into the extracellular space. We determined that new endocannabinoids derived from exogenous anandamide or arachidonic acid were synthesized and released from RBL‐2H3 cells in response to ionomycin. Treatment of RBL‐2H3 cells with nystatin and progesterone, agents that disrupt organization of lipid raft/caveolae, resulted in the attenuation of anandamide and 2‐arachidonyl glycerol synthesis and/or release in response to stimulation with ionomycin suggesting a role for these membrane microdomains in endocannabinoid biosynthesis. Furthermore, anandamide synthesis may be independent ofN‐acyl phosphatidylethanolamine phospholipase D as expression of the enzyme was not detected in RBL‐2H3 cells. We also established that extracellular calcium is necessary for endocannabinoid biosynthesis because release of intracellular calcium stores alone does not promote endocannabinoid biosynthesis. Next, we examined the role of calcium as a ‘switch’ to activate the synthesis of anandamide and simultaneously reduce uptake. Indeed, [3H] anandamide uptake was reduced in the presence of calcium. Our findings suggest a mechanism indicative of calcium‐modulated activation of anandamide synthesis and simultaneous termination of uptake.
Mexiletine for Refractory Chronic Daily Headache: A Report of Nine Cases
Authors: Marmura Michael J. , Passero Frank C. , Young William B.
Published: September 2008

Objective.— To describe the use of mexiletine in the treatment of chronic daily headache in a refractory headache population.

Background.— Intravenous lidocaine is a novel treatment for chronic daily headache with medication overuse and SUNCT syndrome. Mexiletine is a similar but orally active anti‐arrhythmic that has been demonstrated to be an effective analgesic in various types of neuropathic pain. We looked at mexiletine as a preventative treatment for headache in refractory patients.

Methods.— We reviewed the medical records of all patients with an order for mexiletine. For each patient, we determined diagnosis, presence of medication overuse on initial evaluation, pain scores, and if the patient received intravenous lidocaine before starting the medication. We then contacted patients by phone to confirm their dose, to review side effects and current pain scores, and to obtain a global impression of effectiveness.

Results.— We identified 9 patients with a chronic daily headache, including chronic migraine or new daily persistent headache, with significant clinical improvement while using mexiletine as a headache preventative. Each patient had failed to respond to multiple preventative and acute treatments. Seven of the 9 rated mexiletine “much more effective” and 2 “more effective” than previous preventative headache medications. The daily dose ranged from 600 mg/day to 1500 mg/day. Side effects were common and occurred in 7 patients. The majority of patients with an order for mexiletine did not respond to treatment or had intolerable side effects.

Discussion.— The preliminary study suggests mexiletine is a useful preventative treatment for some patients with chronic daily headache, including refractory patients with medication overuse or those who have failed multiple preventatives in the past.
Public Views on Drinking Water Standards as Risk Indicators
Authors: Johnson Branden B.
Published: September 2008

Government agencies often compare contaminant levels to standards and other regulatory benchmarks to convey relative risk to public audiences, as well as for enforcement. Yet we know little of how citizens interpret these risk indicators or factors influencing interpretations. Owners of private residential wells in New Jersey were surveyed by mail. A majority appreciated this comparison, trusted the standard, and could effectively compare the contaminant level to the standard. Most people who recalled that their own well water quality was unsatisfactory simply installed treatment systems. However, there was also a surprising amount of inability to tell whether pollution levels were better or worse than the standard, perhaps exacerbated by confusing institutional language to summarize the comparison (e.g., pollution “exceeds” or is “less than” the standard) and innumeracy. There was also substantial skepticism about the degree to which pollution levels below, or (to a lesser extent) above, the standard are harmless or harmful, respectively. Skepticism was variously due to distrust of standards, disbelief in thresholds for health effects, inability to accurately compare standards and contaminant levels, information processing, and demographics. Discontinuity in reactions below versus above the standard did not exist in the aggregate, and rarely among individuals, contrary to some previous findings. At identical standards and contaminant levels, familiar toxins (mercury, arsenic, lead) elicited higher risk ratings than less familiar ones. Given the wide institutional use of this risk indicator, further research on how to improve the design and use of this indicator, and consideration of alternatives, is warranted.
How Does Financing Impact Investment? The Role of Debt Covenants
Authors: CHAVA SUDHEER , ROBERTS MICHAEL R.
Published: September 2008

We identify a specific channel (debt covenants) and the corresponding mechanism (transfer of control rights) through which financing frictions impact corporate investment. Using a regression discontinuity design, we show that capital investment declines sharply following a financial covenant violation, when creditors use the threat of accelerating the loan to intervene in management. Further, the reduction in investment is concentrated in situations in which agency and information problems are relatively more severe, highlighting how the state‐contingent allocation of control rights can help mitigate investment distortions arising from financing frictions.
Default and Recovery Implicit in the Term Structure of Sovereign CDS Spreads
Authors: PAN JUN , SINGLETON KENNETH J.
Published: September 2008

This paper explores the nature of default arrival and recovery implicit in the term structures of sovereign CDS spreads. We argue that term structures of spreads reveal not only the arrival rates of credit events , but also the loss rates given credit events. Applying our framework to Mexico, Turkey, and Korea, we show that a single‐factor model with following a lognormal process captures most of the variation in the term structures of spreads. The risk premiums associated with unpredictable variation in are found to be economically significant and co‐vary importantly with several economic measures of global event risk, financial market volatility, and macroeconomic policy.
Nevi with site‐related atypia: a review of melanocytic nevi with atypical histologic features based on anatomic site
Authors: Hosler Gregory A. , Moresi Jean Margaret , Barrett Terry L.
Published: September 2008

A subset of melanocytic nevi share features with melanoma and nevi with architectural disorder but are biologically inert and to date do not appear to portend an increased risk for the development of malignancy. These benign nevi with certain atypical histologic features cluster among specific anatomic sites and are thus designated nevi with site‐related atypia. We categorize these lesions into four main groups: acral, genital, special site and conjunctival, based on anatomy and relative prevalence of specific atypical histologic features. As the literature and our recognition of these lesions continue to grow, our understanding of their biology has not kept pace.
Expression levels of apoptosis‐related proteins and Ki‐67 in nasal NK / T‐cell lymphoma
Authors: Yasuda Hajime , Sugimoto Koichi , Imai Hidenori , Isobe Yasushi , Sasaki Makoto , Kojima Yuko , Nakamura Shinji , Oshimi Kazuo
Published: September 2008

Objectives:  Nasal natural killer (NK)/T‐cell lymphoma is characterized by chemo‐resistance, angiodestruction, and aggressive tumor progression. Few studies exist on molecular characteristics of this disease entity.

Methods:  Expression levels of major apoptosis‐related proteins Bcl‐2, Bcl‐x, Mcl‐1, Bax, and a proliferative marker Ki‐67 were analyzed in 11 nasal NK/T‐cell lymphoma cases by immunohistochemical methods. Nine cases were of NK‐cell lineage and two cases were of T‐cell lineage. For comparison, 12 follicular lymphoma (FL) cases and 16 diffuse large B‐cell lymphoma (DLBCL) cases were also studied.

Results and conclusions:  Bax expression was low in all nasal NK‐cell lymphoma cases, which constitute the major population of nasal NK/T‐cell lymphoma. Bax expression in nasal NK‐cell lymphoma was similar to FL and significantly lower compared with DLBCL. Bcl‐2 expression was significantly lower in nasal NK/T‐cell lymphoma compared with that of FL and DLBCL. Bcl‐x expression was high in all three lymphomas. Two distinct Mcl‐1 expression groups existed for nasal NK/T‐cell lymphoma (6.2 ± 5.2% and 59.1 ± 12.3%, 95% CI). Ki‐67 expression was high in nasal NK/T‐cell lymphoma, and worse prognostic groups tended to express higher levels of Ki‐67. The results suggest a combination of impaired apoptosis and aggressive proliferation in nasal NK/T‐cell lymphoma, and may provide explanations for its poor prognosis.
Porous red cell ultrastructure and loss of membrane asymmetry in a novel case of hemolytic anemia
Authors: Banerjee Debasis , Saha Sutapa , Basu Sumanta , Chakrabarti Abhijit
Published: September 2008

Transmission electron microscopic study revealed large pores on the erythrocyte ghost membranes, disrupted cytoskeleton and microcytosis of circulating erythrocytes in a novel case of hemolytic anemia. Greater loss of phosphatidylserine (PS) asymmetry was observed in younger erythrocytes compared with the aged ones in contrast to the normal red cells. Levels of sialylated glycoconjugates, such as glycophorin, measured by the binding of wheat germ agglutinin, showed greater loss upon aging. Such drastic loss of PS asymmetry leads to faster eryptosis, mediated by shedding of glycophorin‐containing microvesicles leaving highly PS‐exposed erythrocytes accessible to the phagocytes.
A complex t(1;22;11)(q44;q13;q23) translocation causing MLL‐p300 fusion gene in therapy‐related acute myeloid leukemia
Authors: Ohnishi Hiroaki , Taki Tomohiko , Yoshino Hiroshi , Takita Junko , Ida Kohmei , Ishii Masami , Nishida Kazuhiro , Hayashi Yasuhide , Taniwaki Masafumi , Bessho Fumio , Watanabe Takashi
Published: September 2008

The p300 protein shows a striking homology with cyclic‐AMP‐response‐element‐binding‐protein binding protein (CBP) and both proteins form a family of DNA‐binding transcriptional coactivators/histone acetyltransferases. The authors, herein, report a therapy‐related acute myeloid leukemia with MLL‐p300 fusion gene. Spectral karyotyping clarified that chromosome 11 is involved in complex t(1;22;11)(q44;q13;q23), and is fused to the chromosome 22, and direct sequencing revealed the fusion of exon 8 of MLL and exon 15 of p300 in this case. This is only the second reported case of leukemia with an MLL‐p300 fusion gene, and the other case with MLL‐p300 was also a therapy‐related leukemia. Considering that the MLL‐CBP fusion gene is also found almost exclusively in therapy‐related leukemia, the association of MLL‐p300 and MLL‐CBP with therapy‐related leukemia rather than de novo leukemia is thereby suggested.
N‐ and O‐Glycans Are Not Directly Involved in the Oligomerization and Apical Sorting of GPI Proteins
Authors: Catino Maria A. , Paladino Simona , Tivodar Simona , Pocard Thomas , Zurzolo Chiara
Published: September 2008

Oligomerization of glycosyl‐phosphatidylinositol‐anchored proteins (GPI‐APs) into high molecular weight complexes is an essential step for their apical sorting in polarized epithelial cells. However, the mechanism by which apical GPI‐APs oligomerize is still unclear. To investigate the possible role of N‐ and O‐glycosylation, we have analysed the behaviour of two glycosylated GPI‐anchored apical proteins, p75GPI and placental alkaline phosphatase (PLAP), and their glycosylation mutants. We found that both the N‐ and O‐glycosylation mutants are apically sorted, associate to detergent‐resistant microdomains and are able to oligomerize, like the wild‐type proteins, suggesting that glycosylation does not have a direct role in GPI‐AP oligomerization and apical sorting. Interestingly, when cells are depleted of cholesterol and treated with tunicamycin, treatments that by themselves do not affect PLAP sorting, PLAP is not able to oligomerize and is missorted to the basolateral surface, thus supporting an indirect role of N‐glycosylation, possibly mediated by a raft‐associated glycosylated interactor.
Salmonella‐Containing Vacuoles: Directing Traffic and Nesting to Grow
Authors: Bakowski Malina A. , Braun Virginie , Brumell John H.
Published: September 2008

Salmonella enterica serovar Typhimurium (S. typhimurium) is a gram‐negative facultative intracellular pathogen that can infect a broad range of mammalian hosts. Following invasion of host cells, the majority of S. typhimurium are known to reside in a membrane‐bound compartment known as the Salmonella‐containing vacuole (SCV). S. typhimurium actively remodels this compartment using bacterial virulence proteins, called effectors, to establish a protected niche where it can replicate. S. typhimurium delivers more than 30 effectors into the host cell cytosol by bacterial type three secretion systems, encoded by Salmonella pathogenicity island 1 or 2 (SPI‐1 or SPI‐2). Recent studies have revealed a critical role for the SPI‐1 effector SopB in ‘directing traffic’ at early stages of infection, allowing the bacteria to control SCV maturation by modulating its interaction with the endocytic system. At later stages of infection, the SCV establishes a ‘nest’ near the Golgi where optimal bacterial growth takes place. In this study, we highlight these recent developments in our understanding of SCV trafficking.
The Chlamydial Inclusion Preferentially Intercepts Basolaterally Directed Sphingomyelin‐Containing Exocytic Vacuoles
Authors: Moore Elizabeth R. , Fischer Elizabeth R. , Mead David J. , Hackstadt Ted
Published: September 2008

Chlamydiae replicate intracellularly within a unique vacuole termed the inclusion. The inclusion circumvents classical endosomal/lysosomal pathways but actively intercepts a subset of Golgi‐derived exocytic vesicles containing sphingomyelin (SM) and cholesterol. To further examine this interaction, we developed a polarized epithelial cell model to study vectoral trafficking of lipids and proteins to the inclusion. We examined seven epithelial cell lines for their ability to form single monolayers of polarized cells and support chlamydial development. Of these cell lines, polarized colonic mucosal C2BBe1 cells were readily infected with Chlamydia trachomatis and remained polarized throughout infection. Trafficking of (6‐((N‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl) amino)hexanoyl)sphingosine) (NBD‐C6‐ceramide) and its metabolic derivatives, NBD‐glucosylceramide (GlcCer) and NBD‐SM, was analyzed. SM was retained within L2‐infected cells relative to mock‐infected cells, correlating with a disruption of basolateral SM trafficking. There was no net retention of GlcCer within L2‐infected cells and purification of C. trachomatis elementary bodies from polarized C2BBe1 cells confirmed that bacteria retained only SM. The chlamydial inclusion thus appears to preferentially intercept basolaterally‐directed SM‐containing exocytic vesicles, suggesting a divergence in SM and GlcCer trafficking. The observed changes in lipid trafficking were a chlamydia‐specific effect because Coxiella burnetii‐infected cells revealed no changes in GlcCer or SM polarized trafficking.
Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice
Authors: De Castro B. M. , Pereira G. S. , Magalhães V. , Rossato J. I. , De Jaeger X. , Martins‐Silva C. , Leles B. , Lima P , Gomez M. V. , Gainetdinov R. R. , Caron M. G. , Izquierdo I. , Cammarota M. , Prado V. F. , Prado M. A. M.
Published: September 2008

Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild‐type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory.
Characterization of inhibitory mechanism and antifungal activity between group‐1 and group‐2 phytocystatins from taro (Colocasia esculenta)
Authors: Wang Ke‐Ming , Kumar Senthil , Cheng Yi‐Sheng , Venkatagiri Shripathi , Yang Ai‐Hwa , Yeh Kai‐Wun
Published: September 2008

Tarocystatin from Colocasia esculenta, a group‐2 phytocystatin, is a defense protein against phytopathogenic nematodes and fungi. It is composed of a highly conserved N‐terminal region, which is homological to group‐1 cystatin, and a repetitive peptide at the C‐terminus. The purified recombinant proteins of tarocystatin, such as full‐length (FL), N‐terminus (Nt) and C‐terminus (Ct) peptides, were produced and their inhibitory activities against papain as well as their antifungal effects were investigated. Kinetic analysis revealed that FL peptide exhibited mixed type inhibition (Kia = 0.098 μm and Kib = 0.252 μm) and Nt peptide showed competitive inhibition (Ki = 0.057 μm), whereas Ct peptide possessed weak papain activation properties. A shift in the inhibitory pattern from competitive inhibition of Nt peptide alone to mixed type inhibition of FL peptide implied that the Ct peptide has an regulatory effect on the function of FL peptide. Based on the inhibitory kinetics of FL (group‐2) and Nt (group‐1) peptides on papain activity, an inhibitory mechanism of group‐2 phytocystatins and a regulatory mechanism of extended Ct peptide have each been proposed. By contrast, the antifungal activity of Nt peptide appeared to be greater than that of FL peptide, and the Ct peptide showed no effect on antifungal activity, indicating that the antifungal effect is not related to proteinase inhibitory activity. The results are valid for most phytocystatins with respect to the inhibitory mechanism against cysteine proteinase.
Densification, Structure, and Thermophysical Properties of Ytterbium–Gadolinium Zirconate Ceramics
Authors: Liu Zhan‐Guo , Ouyang Jia‐Hu , Zhou Yu , Li Jing , Xia Xiao‐Liang
Published: September 2008

(YbxGd1−x)2Zr2O7 (0≤x≤1.0) ceramic powders synthesized with the chemical‐coprecipitation and calcination method were pressureless‐sintered at 1550–1700°C to develop new thermal barrier oxides with a lower thermal conductivity than yttria‐stabilized zirconia ceramics. (YbxGd1−x)2Zr2O7 ceramics exhibit a defective fluorite‐type structure. The linear thermal expansion coefficients of (YbxGd1−x)2Zr2O7 ceramics increase with increasing temperature from room temperature to 1400°C. The measured thermal conductivity of (YbxGd1−x)2Zr2O7 ceramics first gradually decrease with increasing temperature and then slightly increase above 800°C because of the increased radiation contribution. YbGdZr2O7 ceramics have the lowest thermal conductivity among all the composition combinations studied.
Alumina Optical Surface Heat Shield for Use in Near‐Solar Environment
Authors: King Don E. , Drewry David G. , Sample Jennifer L. , Clemons Dale E. , Caruso Keith S. , Potocki Ken A. , Eng Douglas A. , Mehoke Douglas S. , Mattix Michael P. , Thomas Michael E. , Nagle Dennis C.
Published: September 2008

Experiments indicate that coating a heat shield with alumina can significantly reduce spacecraft temperature during operation near the sun. A thin alumina (Al2O3) coating applied to carbon–carbon (C–C) reflects the majority of the visible solar irradiance while reemitting absorbed energy in the infrared. Testing on Al2O3‐coated C–C coupons using visible and NIR lasers (from ambient to 1773 K) show that the solar‐absorptance‐to‐IR emittance ratio (αS/ɛIR) of the Al2O3‐coated heat shield was 0.6 or less. Compared with an uncoated carbon–carbon heat shield, the coated version is at least 12% cooler, enabling thermal insulation mass reductions, improved scientific measurements, and the use of less exotic thermal protection materials.
A Series of Ethyl 6‐Arylmethoxy‐7‐Alkoxy‐4‐Hydroxy‐3‐Quinolinecarboxylates: Synthesis and Anticoccidial Activity Against Eimeria tenella
Authors: Yan Chun‐Rong , Xu Jian , Weng Ya‐Biao , Li Juan , Wang Yu‐Liang , Chen Hua
Published: September 2008

A series of ethyl 6‐arylmethoxy‐7‐alkoxy‐4‐hydroxy‐3‐quinolinecarboxylates was synthesized as anticoccidial medicine, and their structures were characterized by

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H NMR, MS, and IR spectra. Anticoccidial activities of these compounds were evaluated according to the anticoccidial index method. The results indicated that five of these compounds exhibited anticoccidial activities against Eimeria tenella in the chicken’s diet with a dose of 27 mg/kg. In particular, the anticoccidial index of ethyl 6‐(2,5‐dimethylbenzyloxy)‐7‐methoxy‐4‐hydroxy‐3‐quinolinecarboxylate and ethyl 6‐(2,5‐dimethylbenzyloxy)‐7‐ethoxy‐4‐hydroxy‐3‐quinolinecarboxylate was 169.3 and 175.1, respectively, which indicated that the two compounds have high anticoccidial activity.