bluuebunny/crossref_metadata_2025 huggingface dataset:
Syntheses of (+)‐(S,S)‐(cis‐6‐Methyltetrahydropyran‐2‐yl)acetic acid and of (−)‐(R,R)‐Didesoxy‐pyrenophorine Using a New d5‐Reagent. Preliminary communication
Authors: Seebach Dieter , Phmakotr Manat
Published: December 2004

The Li/K‐derivative6is used to synthesize the title compounds (3aand4a) in enantiomerically pure form from (−)‐(S)‐propylene epoxide. The C,C bond forming key step leading to the hydroxyketone 7 is followed by cyclization (→,8), Beckmann cleavage (→9b) and hydrolysis to3a(recently isolated from civet). Base treatment of3aopens the ring (10) to give the hydroxyacid1which is cyclized to the macrolide4a. The synthetic usefulness of the highly nucleophilic doubly reduced dienone system6as d5‐reagent (see synthons 2) is thus demonstirated.
The Total Synthesis of (±)‐Isocomene by an Intramolecular Ene Reaction. Preliminary communication
Authors: Oppolzer Wolfgang , Bättig Kurt , Hudlicky Tomas
Published: December 2004

The racemic sesquiterpene isocomene (1) has been synthesized starting from 1,7‐octadien‐3‐one (2) in a stereoselective manner (Scheme 2). In the key step 4 → 5 the C(7), C(8)‐bond was formed by an intramolecular thermal ene reaction. Further elaboration of 5 involved the ring contraction 6 → 7, the elimination 8 → 9 and the final olefin isomerization 9 → 1.
A Novel Synthesis of Aporphines via 3‐Phenylphenethylamines
Authors: Gerecke Max , Brossi Arnold
Published: December 2004

rac‐1,2,10‐Trimethoxy‐aporphine (14) and rac‐2‐ethoxy‐10,11‐dimethoxyaporphine (27) have been synthesized from the 3‐phenylphenethylamines 9 and 22 by a new route. The 8‐phenyl‐3,4‐dihydroisoquinolines 11 and 24, the oxo‐aporphines 12 and 25 and the rac‐nor‐aporphines 13 and 26 were obtained as intermediates.
Synthèse de l'hydroxy‐3β‐méthano‐22,23‐nor‐24‐cholestène‐5 pour comparaison avec le cystostérol
Authors: Gülaçlar Fazil O. , Djerassi Carl
Published: December 2004

Synthesis of 22,23‐methano‐24‐nor‐cholest‐5‐en‐3β‐ol and comparison with cystosterol

22,23‐Methano‐24‐nor‐cholest‐5‐en‐3β‐ol, a novel cyclopropane‐containing sterol was synthesized from stigmasterol and found to be different from the isomeric, naturally occurring marine sterol cystosterol.
Notiz über einen Zugang zu β, γ‐ungesättigten Carbonsäurederivaten mit Hilfe der Amidacetal‐Claisenumlagerung. Über synthetische methoden, 17. Mitteilung
Authors: Jenkins Paul Richard , Gut Rudolf , Wetter Hansjürg , Eschenmoser Albert
Published: December 2004

Note on a preparation of β, γ‐unsaturated carboxylic acid derivatives using the amide acetal Claisen rearrangement

3‐(Trimethylsilyl)allyl alcohols smoothly undergo the amide acetal Claisen rearrangement furnishing allyl silanes. Subsequent protolysis with HF at −20° provides a convenient, stereoselective method for the preparation of β, γ‐unsaturated carboxylic acid derivatives. Three model examples illustrate the procedure.
Synthese von 4‐Trichlorsilylmethylbenzonitril und 4‐(2‐Trichlorsilyläthyl)pyridin zur Oberflächenmodifikation von Zinndioxid
Authors: Grüniger Hans‐Rudolf , Calzaferri Gion
Published: December 2004

Synthesis of 4‐Trichlorosilylmethylbenzonitrile and 4‐(2‐Trichlorosilylethyl)pyridine for Surface Modification of Tin Dioxide

We describe the synthesis of 4‐(trichlorosilylmethyl)benzonitrile and 4‐(2‐trichlorosilylethyl)pyridine, starting from 4‐(bromomethyl)benzonitrile and trichlorosilane or vinylpyridine and trichlorosilane. Trimethoxysilanes are obtained by reaction of the trichlorosilyl compounds with methyl orthoformate. 4‐(Trichlorosilylmethyl)benzonitrile and 4‐(2‐trichlorosilylethyl)pyridine are used to modify the surface of tin dioxide.
A New α,β‐Enone → Alkynone Fragmentation. Syntheses of exaltone® and (±)‐muscone
Authors: Fehr Charles , Ohloff Günther , Büchi George
Published: December 2004

p‐Toluenesulfonylhydrazones of α, β‐unsaturated ketones undergo an alkynone fragmentation in high yield when treated with electrophiles under basic conditions. With N‐bromosuccinimide in alcohols, the p‐tosylhydrazones 4a and 4b yielded in a one‐pot reaction the cyclic 4‐alkyn‐1‐ones 5a and 5b; these were converted to Exaltone® (1a) and muscone (1b) on catalytic hydrogenation.
Recherche d'analogues de nucléosides à activité antivirale
Authors: Tronchet Jean M. J. , Valero Miguel J.
Published: December 2004

Search for Antiviral Nucleosides Analogues

In contrast to the reported impossibility of obtaining the expected products when 1‐(2,3‐O‐isopropylidene‐1,5‐dialdoribofurannos‐1‐yl)uracile (2) was treated with stabilized ylides, we prepared in good to excellent yields the modified nucleosides 4–9 by reaction of 2 respectively with acetylmethylidene‐, benzoylmethylidene‐, ethoxymethylidene‐, methoxymethylidene‐, succinimidylidene‐ or N‐phenylsuccinimidylidene‐triphenylphosphorane. Compounds 4–10 were tested against the herpes virus type 1 (HF) and influenza virus A2/Scotland. The modified nucleoside 9 showed a limited but significative activity against the herpes virus.
Polar Effects in the Solvolysis of 4‐Substituted Bicyclo [2.2.2]octyl p‐Nitrobenzenesulfonates. Polar effects. VII
Authors: Grob Cyril A. , Rich Roland
Published: December 2004

Hydrolysis of bicyclo[2.2.2]octylp‐nitrobenzenesulfonate (14a, X = p‐NO2C6H4SO3), and nineteen 4‐R‐substituted derivatives 14b–14t in 70% aqueous dioxane yield the corresponding bicyclo[2.2.2]octanols 14 (X = OH), exclusively. The 7‐center fragmentation to 1,4‐dimethylidene‐cyclohexane (15) is not observed. The logarithms of most of the rate constants, measured in 80% ethanol, correlate well with the corresponding inductive substituent constants σ of R. Hence, in these cases ionization rate is controlled by the inductive effect of R only. Poor correlations result when the substituents are potentially electrofugal groups, such as COO−, CH2OH, CH2NH2, CONH2 and H, the deviations from the inductive regression line corresponding to rate enhancements of 1.6 to 8. These exalted substituent effects are tentatively ascribed to extended hyperconjugation involving two σ‐bonds. This study corroborates previous evidence that the inductive effect alone does not fully account for the polar effect of some substituents in reactions involving carbocations.
Ionophore vom Typ der 3‐Oxapentandiamide
Authors: Pretsch Ernö , Ammann Daniel , Osswald Hans F. , Güggi Mare , Simon Wilhelm
Published: December 2004

Ionophores of the Type of 3‐Oxapentane Diamides

A series of lipophilic 3‐oxapentane diamides were prepared and their selectivity in membranes was studied. N, N, N′, N′‐Tetracyclohexyl‐3‐oxapentane diamide forms 1:2‐ and 1:3‐metal/ligand‐complexes with Mg2+ and Ca2+ respectively and induces a selectivity in membranes for Ca2+ over Mg2+ by a factor of about 104.
Un nouvel exemple de transposition: l'épimérisation en C(3) d'hydroxy‐3‐δ1‐pyrazolines dérivées de sucres
Authors: Tronchet Par Jean M. J. , Martinez‐Munoz Ernesto
Published: December 2004

A Novel Example of Reversible Ring Opening: The Epimerization at C(3) of Sugar 3‐Hydroxy‐Δ1‐pyrazolines

Reaction of 1 (either geometrical isomer) with hydrazine followed by in situ Ag2O oxidation led to two pairs of interconverting isomers 4 ⇄ 5 and 6 ⇄ 7. By the same treatment, (Z)‐10 and (or) (E)‐10 gave the pair 11 ⇄ 12. Acetylation of 4 ⇄ 5 led to a non interconverting mixture of 8 and 9. This fact, and the lack of incorporation of 18O when the epimerization took place in the presence of H218O indicated that the most probable mechanism consisted in a reversible ring opening (D ⇄ E ⇄ F). The kinetic parameters of these reactions are given and structural assignments proposed for the new compounds.
Herstellung, Kristallstruktur und magnetische Eigenschaften von Bis (1,2‐benzochinondiimid)‐1,2‐benzosemichinondiimidokobalt (II)‐tetraphenylborat‐pentahydrat
Authors: Zehnder Margareta , Löliger Hans
Published: December 2004

Synthesis, Crystal Structure, and Magnetic Properties of Bis(1,2‐benzoquinonediimide)‐1,2‐benzosemiquinonediimidocobalt (II)‐tetraphenylborate‐pentahydrate

Co (II)‐salts catalyze the autoxidation of 1,2‐diaminobenzene in slightly alkaline solution. Deeply coloured metal complexes are formed during the reaction suggesting intermediate radical or semiquinonediimide stages of the aromatic ligands. Starting from [CoII (1,2‐diaminobenzene)3] (ClO4)2 two different intermediate complexes can be isolated, the magnetic properties of which point to a high‐spin cobalt (II)‐complex and a low‐spin cobalt (II)‐complex with a radical ligand respectively. The X‐ray structure determination of the latter complex yielded a square pyramidal arrangement, the Co‐N4‐plane distance being only 0.5 Å. The dark blue coloured complex is diamagnetic. Two of the aromatic ligands have the oxidation state of a benzoquinonediimide while the third, coordinated by one amino group only, is pseudosemiquinonoid. Crystals of C42H48BCoN6O5 are monoclinic, a = 14.493 (5), b = 18.341 (7), c = 15.492 (5) Å, β = 99.198 (5), space group P21/n. Dobs. = 1.290, Dcalc. = 1.289 g/cm3 for Z = 4. The structure was solved by Patterson's method and refined by least‐squares techniques to R = 0.088 for 2866 of 5014 independent reflexions.
Total Synthesis of β‐Bulnesene and 1‐Epi‐β‐bulnesene by Intramolecular Photoaddition
Authors: Oppolzer Wolfgang , Wylie Robert D.
Published: December 2004

dl‐β‐Bulnesene (1) and dl‐1‐epi‐α‐bulnesene (15) have been synthesized starting from the bromide 4 (Schemes 2 and 3). In the key step 9→10 the bonds of the final product were formed by an intramolecular photoaddition. The synthesis was completed by the fragmentation 12→14 and the Wittig reaction 14→15+1.
Anil‐Synthese 22. Mitteilung über die Herstellung von Styryl‐und Distyryl‐Derivaten des Pyridins
Authors: Siegrist Adolf Emil , Meyer Hans Rudolf , Gassmann Peter , Moss Serge
Published: December 2004

Preparation of Styryl and Distyryl Derivatives of Pyridine

2,4‐, 2,5‐ and 2,6‐Dimethylpyridines react with anils of aromatic aldehydes in the presence of dimethylformamide and potassium hydroxide to yield the corresponding distyrylpyridines (‘anil synthesis’). Under the same reaction conditions (4‐methylstyryl)pyridines are converted to (stilbenylvinyl)pyridines. Similarly, the Schiff's base derived from pyridine‐3‐carbaldehyde and p‐chloroaniline on treatment with methyl‐ and p‐tolyl‐substituted aromatic heterocycles gives the corresponding (heteroaryl‐styryl)pyridines, whereas with the Schiff's bases derived from pyridine‐2‐ and ‐4‐carbaldehyde side reactions, such as dimerization followed by disproportionation predominate.
(+)‐(1S, 3S, 6S, 8S)‐und (−)‐(1R, 3R, 6R, 8R)‐4, 9‐Twistadien: Synthese und Bestimmung der absoluten Konfiguration
Authors: Capraro Hans‐Georg , Ganter Camille
Published: December 2004

(+)‐(1S, 3S, 6S, 8S)‐and (−)‐(1R, 3R, 6R, 8R)‐4, 9‐Twistadiene: Synthesis and Absolute Configuration

A synthesis and the determination of the absolute configuration of (+)‐(1S, 3S, 6S, 8S)‐ and (−)‐(1R, 3R, 6R, 8R)‐4, 9‐twistadiene ((+)‐ and (−)‐4, respectively) is described. Their chiroptical properties are compared with those of saturated twistane ((+)‐ and (−)‐5) as well as with those of the unsaturated and saturated 2, 7‐dioxatwistane analogs (+)‐ and (−)‐9, and (+)‐ and (−)‐10, respectively, which also are compounds of known absolute configurations.
Different patterns of blood flow response in the trapezius muscle following needle stimulation (acupuncture) between healthy subjects and patients with fibromyalgia and work‐related trapezius myalgia
Authors: Sandberg Margareta , Larsson Britt , Lindberg Lars‐Göran , Gerdle Björn
Published: December 2004

Needle stimulation (acupuncture) has recently been shown to increase blood flow in the tibialis anterior muscle and overlying skin in healthy subjects (HS) and patients with fibromyalgia (FM). The aim of the present study was to examine the effect of needle stimulation on local blood flow in the trapezius muscle and overlying skin in HS and two groups of patients suffering from chronic pain in the trapezius muscle, i.e., FM and work‐related trapezius myalgia (TM) patients. Two modes of needling, deep muscle stimulation (Deep) and subcutaneous needle insertion (SC), were performed at the upper part of the shoulder and blood flow was monitored for 60 min post‐stimulation. Blood flow changes were measured non‐invasively by using a new application of photoplethysmography. Increased blood flow in the trapezius muscle and overlying skin was found in all three groups following both Deep and SC. In HS, Deep was superior to SC in increasing skin and muscle blood flow, whereas in FM, SC was as effective as, or even more effective, than Deep. In the severely affected TM patients, no differences were found between the stimuli, and generally, a lesser blood flow response to the stimuli was found. At Deep, the muscle blood flow increase was significantly larger in HS, compared to the two patient groups. Positive correlations were found between muscle blood flow at Deep and pressure pain threshold in the trapezius muscle, neck movement and pain experienced at the stimulation, and negative correlations were found with spontaneous pain‐related variables, symptom duration and age, pointing to less favorable results with worsening of symptoms, and to the importance of nociceptor activation in blood flow increase. It was hypothesized that the different patterns of muscle blood flow response to the needling may mirror a state of increased sympathetic activity and a generalized hypersensitivity in the patients. The intensity of stimulation should be taken into consideration when applying local needle stimulation (acupuncture) in order to increase the trapezius muscle blood flow in chronic pain conditions.
Complex regional pain syndrome type‐I after rubella vaccine
Authors: Genc Hakan , Karagoz Aynur , Saracoglu Meryem , Sert Ebru , Erdem Hatice Rana
Published: December 2004

Complex regional pain syndrome type I (CRPS‐I) is a complex disorder characterised by pain, autonomic dysfunction, and decreased range of motion. The syndrome was believed as a well‐recognized disorder in adults but, less commonly recognized in children. CRPS‐I after vaccination has been rarely reported. We reported an 11‐year‐old young girl with CRPS‐I due to rubella vaccine.
Opioid tolerance and dependence — do they matter?
Authors: Jage Jürgen
Published: December 2004

The use of opioids has long been accepted as the standard of care in patients with cancer and acute pain. Opioids can further be used effectively in specific subgroups of patients with chronic nonmalignant pain states. While the development of tolerance and physical dependence are known effects of opioids in cancer and noncancer pain populations, these patients can not be regarded as addicted. However, long‐term therapy with short‐acting opioids predisposes to tolerance and addiction.

Recent research has confirmed the important role of psychopathologic and psychosocial conditions as predictors of failed opioid effectiveness in a significant number of noncancer pain subgroups. The clinical picture of failed therapy may be complicated by noncompliance, concealed consumption of psychotropic substances, and diversion of prescribed opioids for various purposes as, e.g., selling for profit, or sharing excess opioids with others.

This article discusses the effects of opioid therapy, including tolerance, physical dependence, drug‐aberrant behavior, drug history, psychopathology, and somatization.
Hippocampal infection with HSV‐1‐derived vectors expressing an NMDAR1 antisense modifies behavior
Authors: Adrover M. F. , Guyot‐Revol V. , Cheli V. T. , Blanco C. , Vidal R. , Alché L. , Kornisiuk E. , Epstein A. L. , Jerusalinsky D.
Published: December 2004

Herpes simplex virus‐derived amplicon vectors simultaneously expressing the open reading frame encoding NR1 subunit of the NMDA receptor, either in sense or antisense orientation, as well as the open reading frame encoding the green fluorescent protein (GFP), as distinct transcription units, were constructed. Vector expression in cells was demonstrated by GFP‐fluorescence, immunofluorescence, Western blots and RT‐PCR. The vectors were inoculated into the dorsal hippocampus of adult male rats, which were then trained for habituation to an open field and for inhibitory avoidance to a foot‐shock. Those animals injected with vectors expressing NR1 protein showed habituation to a new environment, and achieved the criteria for a step‐down inhibitory avoidance to a foot‐shock. In contrast, animals injected with vectors carrying the NR1 open reading frame in antisense position, showed neither habituation nor appropriate performance in the inhibitory avoidance task. There was no evidence for motor impairment or motivational disturbance, since all the animals exhibit similar behavior and performance in the training sessions. Hence, the impaired performance might be due to either amnesia or disability to record events. Transgene expression in brain, as revealed by GFP fluorescence, was mainly observed in pyramidal cells of CA1, but also in CA3. Therefore, our results strongly support the participation of hippocampal NR1 subunit in habituation to a new environment, but also in recording events for the inhibitory avoidance task. Hence, amplicon vectors appear to be useful tools to modify endogenous gene expression at a defined period, in restricted brain regions, and should allow investigating in vivo functions of genes.
Seasonal shifts in nest temperature can modify the phenotypes of hatchling lizards, regardless of overall mean incubation temperature
Authors: Shine R.
Published: December 2004

The thermal regimes experienced by a reptilian egg can influence phenotypic traits (size, sex, shape, locomotor performance, etc.) of the hatchling that emerges from that egg. Natural nests of the oviparous scincid lizard Bassiana duperreyi in the Brindabella Range of south‐eastern Australia show strong seasonal shifts in temperature: first and last weeks of incubation often differ by >5 °C.

Eggs of B. duperreyi were incubated under thermal regimes with identical overall mean values for average temperature and diel range, but differing in the sequence of temperatures. Some eggs were kept at 18 ± 5 °C throughout incubation; others went gradually from cool (16 ± 5 °C) to warm (20 ± 5 °C); and others from warm (20 ± 5 °C) to cool (16 ± 5 °C).

These treatments significantly modified not only incubation periods (stable mean temperatures delayed hatching), but also hatchling traits: progressively decreasing temperatures yielded hatchlings with a higher incidence of deformities, smaller body size, relatively longer tails, and reduced locomotor performance than siblings from increasing temperatures.

Seasonal shifts in incubation temperatures are widespread, and may generate important variation in hatchling phenotypes. Sensitivity to such shifts may influence phenomena such as nest‐site selection, the seasonal timing of nesting, and the evolution of viviparity.
Lamotrigine kidney distribution in male rats following a single intraperitoneal dose
Authors: Castel‐Branco M.M. , Falcão A.C. , Figueiredo I.V. , Macedo T.R.A. , Caramona M.M.
Published: December 2004

As it has been previously shown that lamotrigine (LTG) accumulates in the kidney of male rats, the purpose of the present investigation was to characterize the kidney profiles of LTG and its kidney distribution pattern in male rats, in order to confirm if a preferential distribution exists and to analyse if it does or does not affect the LTG systemic pharmacokinetics. Adult male Wistar rats were intraperitoneally injected with 5, 10 and 20 mg/kg of LTG. The concentration–time profiles of LTG in plasma and whole kidney were determined over 120 h postdose. The distribution of LTG in the rat kidney was investigated in another group of rats by measuring LTG levels in the renal cortex and medulla. The LTG plasma concentration–time profiles revealed a linear relationship with dose. However, a slight increase in the LTG elimination half‐life with dose was observed. In contrast, a nonlinear relationship was established between LTG kidney levels and the dose administered. Consequently, nonparallel patterns were observed between LTG plasma and kidney profiles. The LTG kidney distribution pattern revealed an accumulation of LTG in the renal cortex. The present study demonstrated that LTG distributes preferentially to the kidneys of the male rat in a dose‐dependent manner and suggests that such distribution may slightly affect the systemic kinetics of the drug.
Effect of tempol (4‐hydroxy tempo) on gentamicin‐induced nephrotoxicity in rats
Authors: Karataş Yusuf , Seçilmiş M. Ata , Karayaylalı İbrahim , Doran Figen , Büyükafşar Kansu , Şingirik Ergin , Saglıker Yahya , Dikmen Atilla
Published: December 2004

We investigated the effects of tempol (4‐hydroxy tempo), a membrane‐permeable radical scavenger, on gentamicin‐induced renal failure in rats. The rats were given gentamicin (100 mg/kg/day, i.p., once a day); and gentamicin (100 mg/kg/day, i.p.) and tempol (3.5, 7 or 14 mg/kg/day, i.p., once a day). At the end of 7 days, the gentamicin group produced the remarkable nephrotoxicity, characterized by a significantly decreased creatinine clearance and increased serum creatinine, blood urea nitrogen (BUN) and daily urine volume when compared with controls. In control the BUN value was 21.2 ± 0.07 (mg/100 mL); in comparison, it was 96.9 ± 6.03 in gentamicin group (P < 0.05). Renal histopathologic examination confirmed acute tubular necrosis in this group. In rats treated with gentamicin and tempol a partial improvement in biochemical and histologic parameters was observed. BUN values were 96.9 ± 6.03 and 36.3 ± 2.39 in gentamicin, and gentamicin plus tempol (14 mg/kg) treated groups, respectively (P < 0.05). These results suggest that the administration of tempol may have a protective effect on gentamicin‐induced nephrotoxicity in rats.
Src‐dependent phosphorylation of the EGF receptor Tyr‐845 mediates Stat‐p21waf1 pathway in A431 cells
Authors: Sato Ken‐ichi , Nagao Tomomi , Iwasaki Tetsushi , Nishihira Yusuke , Fukami Yasuo
Published: December 2004

Background:  Cell surface receptor for the epidermal growth factor (EGFR) and cytoplasmic tyrosine kinase c‐Src co‐operate in several cellular functions such as proliferation and apoptosis. Our previous studies have shown that ectopic expression of the adaptor protein p52shc or p66shc, but not p46shc, and EGF stimulation lead to the activation of c‐Src that is accompanied by phosphorylation of signal transducers and activators of transcription (Stat) in A431 cells.

Results:  Here, we show that by using A431 cells as a model system, expression of p52shc, or cell stimulation with EGF or H2O2 leads to phosphorylation of EGFR on Tyr 845 that is located to the activation segment of the catalytic domain. The phosphorylation of Tyr 845 can be inhibited by PP2, but not by AG1478, and is associated with Src activation and Stat 3/5 phosphorylation, but not with MAP (mitogen‐activated protein) kinase phosphorylation. Phosphorylation of Stat 3/5 in response to p52shc expression, EGF or H2O2 could also be inhibited by introduction into cells of phospho‐Tyr 845‐specific antibody or by expression of dominant‐negative version of c‐Src. Co‐incubation of purified c‐Src and EGFR results in phosphorylation of Tyr 845 in vitro, indicating that c‐Src can directly phosphorylate EGFR on Tyr 845.

Conclusion:  These results indicate that multiple signals for c‐Src activation can promote Stat 3/5 phosphorylations through Src‐dependent phosphorylation of EGFR on Tyr 845.
Reach‐ and catchment‐scale determinants of the distribution of freshwater mussels (Bivalvia: Unionidae) in south‐eastern Michigan, U.S.A.
Authors: McRae S. E. , D. Allan J. , Burch J. B.
Published: December 2004

1. We investigated the diversity and distribution of freshwater mussels at 40 sites in an agricultural catchment, the River Raisin in south‐eastern Michigan, to relate mussel assemblages and individual taxa to reach and catchment‐scale variables. Unionids were surveyed by timed searches in 100‐m reaches, and in‐stream and riparian habitat were quantified as well as flow, water chemistry and channel morphology. Land use/cover and surficial geology were determined for site subcatchments and riparian buffers.

2. Some 21 mussel species were found overall; richness ranged from 0 to 12 living species per site. From the upper to middle to lower catchment, the number of individuals, number of species, Shannon–Weaver diversity and relative abundance of intolerant unionids all declined significantly.

3. Four groupings based on overall mussel diversity and abundance were significantly related to reach‐scale habitat variables. The richest mussel assemblages were associated with sites with higher overall habitat quality, greater flow stability, less fine substratum, and lower specific conductance.

4. Stepwise multiple regressions revealed that the distribution and abundance of the total mussel assemblage, as well as the most common species, could be predicted from a combination of reach‐ and catchment‐scale variables (R2 = 0.63 for total mussels, R2 = 0.51–0.86 for individual species).

5. Flow stability, substratum composition and overall reach habitat quality were the most commonly identified reach‐scale variables, and measures of surficial geology were the most effective catchment‐scale variables. The spatial pattern of geology is likely to be responsible for the diversity gradient from the upper to the lower catchment.

6. Prior studies, attempting to explain mussel distributions from local habitat features alone, have found relatively weak relationships. By employing a combination of reach‐ and catchment‐scale habitat variables, this study was able to account for a substantial amount of the spatial variability in mussel distributions.
Virioplankton and microbial communities in aquatic systems: a seasonal study in two lakes of differing trophy
Authors: Bettarel Yvan , Sime‐Ngando Telesphore , Amblard Christian , Carrias Jean‐François , Portelli Christophe
Published: December 2004

1. The seasonal and vertical distribution of the abundance of virus‐like particles (VLPs), together with the abundances of other microbial organisms (bacteria, unpigmented and pigmented nanoflagellates and ciliates), were determined in an oligomesotrophic lake (Pavin, France) and in a eutrophic lake (Aydat, France) between March and December 2000.

2. The abundance of the viral plankton and those of other microbial taxa were significantly higher in the more productive system. The same was for the virus‐to‐bacteria quotient (VBQ), which averaged seven in Lake Pavin and nine in Lake Aydat.

3. The abundance of viruses increased during the period of thermal stratification in both lakes, with the highest values being recorded at the end of summer/early autumn in the epi‐ and the metalimnion. The seasonal pattern of abundance of viruses in both lakes in the surface layer was similar, indicating that the dynamics of viruses may be controlled by environmental factors such as light conditions.

4. There was no correlation between the abundance of viruses and protists. We found correlations between viruses and heterotrophic bacteria in the whole water column in Lake Pavin, but only in the dark bottom waters in Lake Aydat.

5. Overall, the empirical findings in this study lead us to speculate that the weaker correlation between bacteria and viruses in Lake Aydat than in Lake Pavin, as well as the higher VBQ in the former, is a consequence of the increasing relative abundance of non‐bacteriophage VLPs along the trophic gradient of aquatic systems.
Differential role of symbiotic fungi in lignin degradation and food provision for fungus‐growing termites (Macrotermitinae: Isoptera)
Authors: Hyodo F. , Tayasu I. , Inoue T. , Azuma J.‐I. , Kudo T. , Abe T.
Published: December 2004

To investigate whether the role of symbiotic fungi in lignin degradation and food provision differs among fungus‐growing termites (four species of Macrotermes, three species of Odontotermes, Hypotermes makhamensis, Ancistrotermes pakistanicus and Pseudacanthotermes militaris), the chemical composition of fungus combs of different ages and the chitinolytic activity in the gut of termites were analysed. In addition, the carbon stable isotope ratios (δ13C) in old combs, worker termite tissues and fungal nodules (aggregated conidia) were compared.

In Macrotermes spp., the carbohydrate : lignin ratio of the combs increased with increased comb age, but it decreased or remained the same in Odontotermes spp., H. makhamensis, A. pakistanicus and P. militaris. In contrast, the chitin : carbohydrate ratio and ash content increased more over time in the combs of Odontotermes spp., H. makhamensis, A. pakistanicus and P. militaris than in the combs of Macrotermes spp.

Chitinolytic activity in the gut of workers was higher in O. takensis, H. makhamensis and A. pakistanicus than in M. annandalei.

In all species examined, the δ13C value increased in the sequence: old combs < termites < fungal nodules. Based on a two‐source model of δ13C, the contribution of fungi to termite nutrition was considered higher in Odontotermes spp., H. makhamensis, A. pakistanicus and P. militaris than in Macrotermes spp.

These results suggest that symbiotic fungi play different roles among fungus‐growing termites. In Macrotermes spp., the main role of symbiotic fungi is to degrade lignin, so that the termites can utilize cellulose more efficiently, whereas in Odontotermes spp., H. makhamensis, A. pakistanicus and P. militaris, it is to serve as a food source.
The second phase activation of protein kinase C δ at late G1 is required for DNA synthesis in serum‐induced cell cycle progression
Authors: Kitamura Koichi , Mizuno Keiko , Etoh Akiko , Akita Yoshiko , Miyamoto Akitomo , Nakayama Kei‐Ichi , Ohno Shigeo
Published: December 2004

Background: Cell lines that stably over‐express protein kinase C (PKC) δ frequently show a decrease in growth rate and saturation density, leading to the hypothesis that PKCδ has a negative effect on cell proliferation. However, the mode of PKCδ activation, the cell cycle stage requiring PKCδ activity, and the exact role of PKCδ at that stage remains unknown.

Results: Here we show that the treatment of quiescent fibroblasts with serum activates PKCδ at two distinct time points, within 10 min after serum treatment, and for a longer duration between 6 and 10 h. This biphasic activation correlates with the phosphorylation of Thr‐505 at the activation loop of PKCδ. Importantly, an inhibitor of PKCδ, rottlerin, suppresses the biphasic activation of PKCδ, and suppression of the second phase of PKCδ activation is sufficient for the suppression of DNA synthesis. Consistent with this, the transient over‐expression of PKCδ mutant molecules lacking kinase activity suppresses serum‐induced DNA synthesis. These results imply that PKCδ plays a positive role in cell cycle progression. While the over‐expression of PKCδ enhances serum‐induced DNA synthesis, this was not observed for PKCɛ. Similar experiments using a series of PKCδ/ɛ chimeras showed that the carboxyl‐terminal 51 amino acids of PKCδ are responsible for the stimulatory effect. On the other hand, the over‐expression of PKCδ suppresses cell entry into M‐phase, being consistent with the previous studies based on stable over‐expressors.

Conclusions: We conclude that PKCδ plays a role in the late‐G1 phase through the positive regulation of cell‐cycle progression, in addition to negative regulation of the entry into M‐phase.
The receptor tyrosine kinase Ror2 is involved in non‐canonical Wnt5a/JNK signalling pathway
Authors: Oishi Isao , Suzuki Hiroaki , Onishi Nobuyuki , Takada Ritsuko , Kani Shuichi , Ohkawara Bisei , Koshida Ikue , Suzuki Kentaro , Yamada General , Schwabe Georg C. , Mundlos Stefan , Shibuya Hiroshi , Takada Shinji , Minami Yasuhiro
Published: December 2004

Background: Ror2 is an orphan receptor, belonging to the Ror family of receptor tyrosine kinases. Although Ror2 has been shown to play crucial roles in developmental morphogenesis, the precise signalling events that Ror2 mediates remain elusive. Since Ror2 possesses an extracellular cysteine‐rich domain (CRD) that resembles the Wnt‐binding sites of the Frizzled (Fz) proteins, it is conceivable that Ror2 interacts with members of the Wnt family.

Results: Both Ror2−/− and Wnt5a−/− mice exhibit dwarfism, facial abnormalities, short limbs and tails, dysplasia of lungs and genitals, and ventricular septal defects. In vitro binding assay revealed that Wnt5a binds to the CRD of Ror2. Furthermore, Ror2 associates via its CRD with rFz2, a putative receptor for Wnt5a. Interestingly, Wnt5a and Ror2 activate the non‐canonical Wnt pathway, as assessed by activation of JNK in cultured cells and inhibition of convergent extension movements in Xenopus.

Conclusions: Our findings indicate that Wnt5a and Ror2 interact physically and functionally. Ror2 may thus act as a receptor for Wnt5a to activate non‐canonical Wnt signalling.
Carbon emissions from fires in tropical and subtropical ecosystems
Authors: VAN DER WERF GUIDO R. , RANDERSON JAMES T. , COLLATZ G. JAMES , GIGLIO LOUIS
Published: December 2004

Global carbon emissions from fires are difficult to quantify and have the potential to influence interannual variability and long‐term trends in atmospheric CO2 concentrations. We used 4 years of Tropical Rainfall Measuring Mission (TRMM) Visible and Infrared Scanner (VIRS) satellite data and a biogeochemical model to assess spatial and temporal variability of carbon emissions from tropical fires. The TRMM satellite data extended between 38°N and 38°S and covered the period from 1998 to 2001. A relationship between TRMM fire counts and burned area was derived using estimates of burned area from other satellite fire products in Africa and Australia and reported burned areas from the United States. We modified the Carnegie‐Ames‐Stanford‐Approach (CASA) biogeochemical model to account for both direct combustion losses and the decomposition from fire‐induced mortality, using both TRMM and Sea‐viewing Wide Field of view Sensor (SeaWiFS) satellite data as model drivers. Over the 1998–2001 period, we estimated that the sum of carbon emissions from tropical fires and fuel wood use was 2.6 Pg C yr−1. An additional flux of 1.2 Pg C yr−1 was released indirectly, as a result of decomposition of vegetation killed by fire but not combusted. The sum of direct and indirect carbon losses from fires represented 9% of tropical and subtropical net primary production (NPP). We found that including fire processes in the tropics substantially alters the seasonal cycle of net biome production by shifting carbon losses to months with low soil moisture and low rates of soil microbial respiration. Consequently, accounting for fires increases growing season net flux by ∼12% between 38°N and 38°S, with the greatest effect occurring in highly productive savanna regions.
Living on the edge – plants and global change in continental and maritime Antarctica
Authors: Robinson Sharon A. , Wasley Jane , Tobin Alyson K.
Published: December 2004

Antarctic terrestrial ecosystems experience some of the most extreme growth conditions on Earth and are characterized by extreme aridity and subzero temperatures. Antarctic vegetation is therefore at the physiological limits of survival and, as a consequence, even slight changes to growth conditions are likely to have a large impact, rendering Antarctic terrestrial communities sensitive to climate change.

Climate change is predicted to affect the high‐latitude regions first and most severely. In recent decades, the Antarctic has undergone significant environmental change, including the largest increases in ultraviolet‐B (UV‐B; 290–320 nm) radiation levels in the world and, in the maritime region at least, significant temperature increases. This review describes the current evidence for environmental change in Antarctica, and the impacts of this change on the terrestrial vegetation. This is largely restricted to cryptogams, such as bryophytes, lichens and algae; only two vascular plant species occur in the Antarctic, both restricted to the maritime region. We review the range of ecological and physiological consequences of increasing UV‐B radiation levels, and of changes in temperature, water relations and nutrient availability. It is clear that climate change is already affecting the Antarctic terrestrial vegetation, and significant impacts are likely to continue in the future. We conclude that, in order to gain a better understanding of the complex dynamics of this important system, there is a need for more manipulative, long‐term field experiments designed to address the impacts of changes in multiple abiotic factors on the Antarctic flora.
Acquired haemophilia: experience of two Italian centres with 17 new cases
Authors: Di Bona E. , Schiavoni M. , Castaman G. , Ciavarella N. , Rodeghiero F.
Published: December 2004

Summary. Acquired haemophilia is a rare but often catastrophic haemorrhagic disorder associated with a high mortality rate. No single therapeutic approach has been consistently successful and clinical experience remains mainly anecdotal. This report describes 17 new cases diagnosed at two Italian haemophilia centres between 1979 and 1995.

There was no difference in sex distribution. Mean age at diagnosis was 50 years. Fifty‐nine per cent of cases had associated disorders and 29% developed an inhibitor post‐partum. Eleven (64%) patients required substitutive therapy. Desmopressin was successfully used in five cases for minor bleeding. Immunosuppressive drugs (steroid, cyclophosphamide or experimental therapy) were used in 14 (82%) cases. Eight of 15 (52%) evaluable cases achieved complete remission (four post‐partum). Fatal haemorrhage occurred in 2/15 (13%) of patients within 2 days from diagnosis.

Acquired haemophilia is a severe coagulopathy. Prompt diagnosis with characterization and intensive treatment is usually required. However, particular subsets of patients such as those with inhibitor occurring post‐partum or with low inhibitor titre at diagnosis usually show a more favourable clinical outcome.
Safety and potential usefulness of liver biopsy in HIV‐seropositive haemophiliacs employing a transjugular venous approach
Authors: GUPTA R. , DRUY E. M. , KESSLER C. M.
Published: December 2004

Summary. Chronic liver disease has affected a majority of haemophiliacs exposed to factor VIII and factor IX concentrates before effective viral attenuation techniques were introduced. Progressive hepatitis and liver failure have increasingly become causes of morbidity, especially in haemophilia patients also seropositive for HIV. Encouraging reports of recombinant alpha interferon to reverse the histological, laboratory and clinical deterioration of chronic active hepatitis justifies obtaining liver biopsies to assess the severity of liver damage; however, the percutaneous method carries a significant risk of bleeding. Therefore, we employed a transjugular venous approach for liver biopsies in six HCV‐, HBSAb‐ and HIV‐seropositive adults with severe haemophilia A (n = 5) or B (n = 1) with persistent liver function abnormalities. Adequacy of the specimens and lack of haemorrhagic complications leads us to conclude that this procedure appears to be safe and effective in individuals with severe haemophilia or other congenital or acquired coagulopathies.
Safer and much cheaper circumcision using fibrin glue in severe haemophilia
Authors: KAVAKLI K. , NISLI G. , OZCAN C. , AVANOGLU A. , ULMAN I. , GOKDEMIR A. , POLAT A. , AYDINOK Y.
Published: December 2004

Summary. Circumcision is a traditional ceremony for Muslims and Jewish people. In order to reduce the high cost of factor concentrates, we administered locally manufactured heat‐treated fibrin glue during operation. Circumcision can be performed safely and is much cheaper using fibrin glue plus a small amount of factor concentrates.
Use of central venous catheters in children with haemophilia: one haemophilia treatment centre experience
Authors: Warrier I. , Baird‐Cox K. , Lusher J. M.
Published: December 2004

Summary. We report our clinic experience with central venous catheters (CVCs) in 23 children with haemophilia, who, in total, had 35 catheters. Seventeen of the 23 children had Broviac catheters (external), 6/23 had an implantable device (Port‐A‐Cath) only, while four had Broviac and Port‐A‐Cath at different times. The age of the patients at the time of initial catheter placement ranged from 4 months to 18 years; 11 were under age 3 years. Indications for CVC placement included induction of immune tolerance, treatment of HIV‐related complications, prophylactic therapy following intracranial haemorrhage, primary prophylaxis and secondary prophylaxis. Catheter‐related infection was the most common complication, occurring in 84% of the external catheters. Of these infections 79% occurred in HIV‐negative subjects. Staph and strep species were the most common infectious organisms isolated. Minor bleeding around the catheter occurred in 20% of cases even with adequate correction of haemophilia. Three children accidentally removed the external catheter (12%). Thrombosis of the catheter was uncommon (8%), occurring in only two patients, one of whom had a small newborn size external catheter. When presenting with line sepsis, haemophilic children who were HIV negative had transient temperature spikes approximately 1 h after catheter flushing. This presentation was different from our oncology or HIV‐positive patients with CVC‐related sepsis. Our experience with ports (Port‐A‐Cath) in haemophilic children is limited, but catheter‐related infection (40%) seems to be less of a problem with the implantable device and the ports have been well accepted by our haemophilic patients and their parents.
Medical, reproductive and psychosocial experiences of women diagnosed with von Willebrand's disease receiving care in haemophilia treatment centres: a case–control study
Authors: Kirtava A. , Drews C. , Lally C. , Dilley A. , Evatt B.
Published: December 2004

Summary.Objective: To assess the medical, gynaecological and reproductive experiences of women with von Willebrand's disease (VWD) and to evaluate the impact of VWD on mental health and life activities.

Methods:A total of 102 women with VWD who were registered in haemophilia treatment Centres (HTCs) in the United States and 88 controls were interviewed regarding medical, gynaecological and reproductive history, life activities and symptoms of depression. Symptoms of depression were measured using the Center for Epidemiological Studies Depression Scale (CES‐D).

Results:Excessive bleeding symptoms were reported in 74% of VWD cases compared with 6% of controls. Women with VWD had a higher prevalence of menorrhagia, excessive postpartum bleeding, other gynaecological conditions, arthritis and migraine headaches than did controls. More VWD cases than controls reported that menstruation had a negative impact on overall life activities. No difference in the prevalence of depression was found between cases and controls.

Discussion:Women with VWD experience menorrhagia and other gynaecological conditions at a higher frequency than women without bleeding disorders. Menstruation in women with VWD has a negative impact on life activities. The prevalence of depression was not elevated in this group of women whose VWD is being managed in an HTC.
Development and evaluation of a breast cancer prevention decision aid for higher‐risk women
Authors: Stacey Dawn , O'Connor Annette M. , DeGrasse Cathy , Verma Shailendra
Published: December 2004

Objective  To develop and evaluate the effectiveness of a breast cancer prevention decision aid for women aged 50 and older at higher risk of breast cancer.

Design  Pre‐test–post‐test study using decision aid alone and in combination with counselling.

Setting  Breast Cancer Risk Assessment Clinic.

Participants  Twenty‐seven women aged 50–69 with 1.66% or higher 5‐year risk of breast cancer.

Intervention  Self‐administered breast cancer prevention decision aid.

Main outcome measures  Acceptability; decisional conflict; knowledge; realistic expectations; choice predisposition; intention to improve life‐style practices; psychological distress; and satisfaction with preparation for consultation.

Results  The decision aid alone, or in combination with counselling, decreased some dimensions of decisional conflict, increased knowledge (P < 0.01), and created more realistic expectations (P < 0.01). The aid in combination with counselling, significantly reduced decisional conflict (P < 0.01) and psychological distress (P < 0.02), helped the uncertain become certain (P < 0.02), and increased intentions to adopt healthier life‐style practices (P < 0.03). Women rated the aid as acceptable, and both women and practitioners were satisfied with the effect it had on the counselling session.

Conclusion  The decision aid shows promise as a useful decision support tool. Further research should compare the effect of the decision aid in combination with counselling to counselling alone.
Overcoming the challenges to consumer involvement in cancer research
Authors: Stevens Tony , Wilde David , Hunt John , Ahmedzai Sam H
Published: December 2004

Introduction  Within the last decade, there have been many government initiatives to promote consumer involvement in research, especially in cancer. At the same time, the number and influence of consumer groups themselves have expanded. However, the organizational infrastructure necessary to facilitate consumer involvement has not been developed. Consequently, consumer involvement has tended to remain essentially localized and project driven, with no strategic or regional lead.

Opportunities for involvement and identification of consumers  The opportunities for consumers to influence the research process at each stage of the research process are identified. The different types of consumer involvement are also examined. Novel ways of identifying and recruiting consumers that have been adopted by one cancer network are discussed.

The strategies used in one cancer network  An organizational model designed by one cancer network for involving consumers in research is illustrated. Three innovations are examined in detail. First, how three open consumer conferences have increased awareness of research among service users. Second, the recruitment of consumers to sit on project steering groups and a committee that provides a strategic overview of current research. Third, the establishment of a Consumer Panel for Research where reimbursed, trained consumers are able to provide a considered consumer perspective in a range of settings.

Conclusions  Cancer networks need to take the lead in the development of an organizational infrastructure to facilitate consumer involvement. The model developed in Sheffield could be generalizable to other diseases and other health‐care settings.