bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocannabinoids protect the rat isolated heart against ischaemia
Authors: Lépicier Philippe , Bouchard Jean‐François , Lagneux Caroline , Lamontagne Daniel
Published: June 2003

The purpose of this study was to determine whether endocannabinoids can protect the heart against ischaemia and reperfusion.

Rat isolated hearts were exposed to low‐flow ischaemia (0.5–0.6 ml min−1) and reperfusion. Functional recovery as well as CK and LDH overflow into the coronary effluent were monitored. Infarct size was determined at the end of the experiments. Phosphorylation levels of p38, ERK1/2, and JNK/SAPK kinases were measured by Western blots.

None of the untreated hearts recovered from ischaemia during the reperfusion period. Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2‐arachidonoylglycerol (2‐AG), but not anandamide (up to 1 μM), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH. PEA and 2‐AG also reduced infarct size.

The CB2‐receptor antagonist, SR144528, blocked completely the cardioprotective effect of both PEA and 2‐AG, whereas the CB1‐receptor antagonist, SR141716A, blocked partially the effect of 2‐AG only. In contrast, both ACEA and JWH015, two selective agonists for CB1‐ and CB2‐ receptors, respectively, reduced infarct size at a concentration of 50 nM.

PEA enhanced the phosphorylation level of p38 MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580, and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC inhibitor, chelerythrine.

In conclusion, endocannabinoids exert a strong cardioprotective effect in a rat model of ischaemia–reperfusion that is mediated mainly through CB2‐receptors, and involves p38, ERK1/2, as well as PKC activation.

British Journal of Pharmacology (2003) 139, 805–815. doi:10.1038/sj.bjp.0705313
Two novel mutations in the gene encoding thyroxine‐binding globulin (TBG) as a cause of complete TBG deficiency in Taiwan
Authors: Su Ching‐Chieh , Wu Yi‐Chi , Chiu Chih‐Yang , Won Justin Ging‐Shing , Jap Tjin‐Shing
Published: June 2003

objective Thyroxine‐binding globulin (TBG) encoded by the TBG gene on chromosome Xq22 is the major transport protein, carrying approximately 75% of circulating T4. Inherited defects in TBG are associated with three phenotypes based on the level of TBG in serum of affected hemizygous males: complete TBG deficiency (TBG‐CD), partial TBG deficiency (TBG‐PD) and TBG excess (TBG‐E). In this study, we report two unrelated Han Chinese males with complete TBG deficiency who carry different mutations in the TBG gene.

patients Two index cases of Han males who were diagnosed as having TBG deficiency on the basis of undetectable serum TBG and an additional 75 (50 males and 25 females) normal Han Chinese.

measurement Serum thyroid hormones were measured by chemiluminescent immunoassay, thyroid autoantibodies by an agglutination test, and TSH receptor antibody and TBG by radioimmunoassay. Genomic DNA extraction, polymerase chain reaction (PCR) and DNA sequence analysis of the TBG gene were performed with standard methods.

results One index case had one missense mutation in his copy of the gene, a G → A transition in codon 52 that results in the replacement of serine by asparagine, and a known polymorphism in codon 283 (TTG → TTt) that results in the replacement of leucine by phenylalanine. The allelic frequency of TBG‐Poly allele in 75 normal Han Chinese (100 chromosomes) was 31%. A second index case was hemizygous for a nonsense mutation in codon 280 of exon 3 (TGG → TGa). This mutation, located in the C‐terminal of TBG, predicts a markedly truncated protein.

conclusions This is the first report of complete thyroxine‐binding globulin deficiency (TBG‐CDT1 and TBG‐CDT2) due to TBG gene mutations in Taiwan.
Effects of low‐iodide diet on postsurgical radioiodide ablation therapy in patients with differentiated thyroid carcinoma
Authors: Pluijmen Maurice J. H. M. , Eustatia‐Rutten Carmen , Goslings Bernard M. , Stokkel Marcel P. , Arias Alberto M. Pereira , Diamant Michaela , Romijn Johannes A. , Smit Jan W. A.
Published: June 2003

objective Most patients with differentiated thyroid carcinoma (DTC) undergo total thyroidectomy followed by routine radioiodide thyroid remnant ablation. Most centres that routinely perform radioiodide ablation prescribe a low‐iodide diet (LID) to increase the radioiodide accumulation in thyroid remnants. The efficacy of an LID on thyroid remnant ablation, however, has never been demonstrated convincingly.

design and methods In a retrospective study, we studied two groups of DTC patients without distant metastases, who had received either a standard diet or an LID during ablation (LID group, n = 59, and control group, n = 61). Both groups were compared for radioiodide uptake in thyroid remnants during ablation and efficacy parameters of remnant ablation, 6 months after ablation. A subgroup without extrathyroidal tumour growth was analysed separately (stages T1–3, N0).

results In the total group, the LID during ablation decreased the 24‐h urinary iodide excretion to 26·6 µg compared with 158·8 µg in controls whereas radioiodide uptake in thyroid remnants was increased by 65% (P < 0·001). Six months after ablation, patients were investigated after thyroid hormone withdrawal. In the total group, no significant effects of the LID during ablation were observed on thyroglobulin (Tg) or the percentage of patients with persistent neck activity after 185 MBq 131I. However, in the LID group, 65% of patients without Tg antibodies had undergone successful ablation (defined by absent neck activity and Tg < 2 µg/l) compared with 48% in the control group (P < 0·001). In the subgroup (T1–3, N0), 8% of the patients who had undergone the LID had Tg ≥ 2 µg/l vs. 32% in the control group (P = 0·012), whereas successful ablation was achieved in 71% of patients without Tg antibodies in the LID vs. 45% in the control group (P < 0·001).

conclusion We conclude from this study that a low‐iodide diet during thyroid remnant ablation improves the efficacy of this treatment.
GH‐secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23–24
Authors: Yamasaki Hiroyuki , Mizusawa Noriko , Nagahiro Shinji , Yamada Shozo , Sano Toshiaki , Itakura Mitsuo , Yoshimoto Katsuhiko
Published: June 2003

objective The molecular events leading to the development of GH‐secreting pituitary tumours remain largely unknown. Gsα (GNAS1) mutations are found in 27–43% of sporadic GH‐secreting adenomas in the Caucasian population, but the frequency of GNAS1 mutations in Japanese and Korean acromegalic patients was reported to be lower, 4–9% and 16%, respectively. Other genes responsible for the tumourigenesis of GH‐secreting pituitary adenomas have not been detected yet. PRKAR1A, which codes for the RIα regulatory subunit of cyclic AMP‐dependent protein kinase A (PKA) on 17q23–24, was recently reported to contain inactivating mutations in some Carney complex families, which involved GH‐secreting adenomas in about 10%. We re‐evaluated the frequency of GNAS1 mutations and investigated PRKAR1A on the hypothesis that it might play a role in the tumourigenesis of GH‐secreting adenomas.

design We analysed exons 8 and 9 of GNAS1 and all exons and the exon–intron boundaries of PRKAR1A with the PCR and by direct sequencing using genomic DNA extracted from 32 GH‐secreting pituitary adenomas (30 GH‐secreting adenomas, two GH and PRL‐secreting adenomas) and 28 corresponding peripheral blood samples, and performed loss of heterozygosity (LOH) analysis of 17q23–24 with four microsatellite markers and intragenic markers of PRKAR1A.

results Seventeen of 32 (53·1%) tumours showed somatic‐activating mutations of GNAS1: 16 (53·3%) of 30 GH‐secreting adenomas and one of two GH and PRL‐secreting adenomas. Neither inactivating somatic mutations of PRKAR1A nor LOH of 17q23–24 were detected in any of the tumours examined.

conclusion We reconfirm the important role of activating mutations of GNAS1 in GH‐secreting adenomas, and conclude that PRKAR1A does not play a significant role in the tumourigenesis.
Microsatellite variation within and among North American lineages of Phragmites australis
Authors: Saltonstall K.
Published: June 2003

Over the past century, the spread of the common reed (Phragmites australis) has had a dramatic impact on wetland communities across North America. Although native populations of Phragmites persist, introduced invasive populations have dominated many sites and it is not clear if the two types can interbreed. This study compares patterns of differentiation in 10 microsatellite loci among North American and European Phragmites individuals with results obtained from sequencing of noncoding chloroplast DNA. Three population lineages (native, introduced and Gulf Coast) were previously identified in North America from chloroplast DNA and similar structuring was found in the nuclear genome. Each lineage was distinguished by unique alleles and allele combinations and the introduced lineage was closely related to its hypothesized source population in Europe. Size homoplasy and diagnostic base substitutions distinguishing lineages were evident at several loci, further emphasizing that native, introduced and Gulf Coast North American Phragmites lineages are genetically distinct. Gene flow between lineages was low and invasive introduced populations do not represent a hybrid population type.
Historical biogeography of the catfish genus Hypostomus (Siluriformes: Loricariidae), with implications on the diversification of Neotropical ichthyofauna
Authors: Montoya‐Burgos J. I.
Published: June 2003

Tropical South America possesses the largest ichthyofauna of any continental region. To test whether palaeohydrological changes may have been the causes of such diversification, the ‘hydrogeological’ hypothesis, the phylogenetic relationships of 51 representatives of the catfish genus Hypostomus (Siluriformes: Loricariidae) were inferred using mitochondrial D‐loop haplotype sequences. Specimens were collected in all main tropical South American rivers systems east to the Andes. The major interrelationships found with the D‐loop data were confirmed with a subset of 21 species using complete internal transcribed spacer (ITS) region sequences. The phylogenetic analysis indicate that the genus Hypostomus can be divided into four monophyletic clades. The historical biogeographical analysis of each of these clades allows the identification of seven major cladogenetic events. Using calibrated D‐loop and ITS molecular clocks, date estimations were attributed to each of these cladogenetic events allowing a linkage between four of them with documented hydrogeological changes. Comparisons with published distribution patterns of unrelated fish groups indicate that several of the reconstructed and dated hydrogeological–cladogenetic events may have acted at a large scale on the diversification of Neotropical freshwater fish fauna during late Tertiary.
Parental tracking in the postfire wood decay ascomycete Daldinia loculata using highly variable nuclear gene loci
Authors: Guidot A. , Johannesson H. , Dahlberg A. , Stenlid J.
Published: June 2003

The origin of the male and female gametes involved in fertilization events within a local population of the postfire wood decay ascomycete Daldinia loculata was investigated by genotyping the mycelia growing in the wood and the sexual ascospores, using three highly variable nuclear gene loci. The study was conducted in a geographically isolated burned forest site in southern Sweden. An intensive sampling was performed by collecting stromata containing ascospores and wood samples containing mycelia. In total, from 32 mapped burned birches, cultures of 22 haploid genets from decayed wood and six ascospores from each of 19 stromata were isolated and analysed. In 80% of the investigated burned branches, only one genet was found. From the analysis of the ascospore genotypes, we detected 30 fertilization events and 60% of them were the result of mating between conidia (clonal propagules) acting as male gametes and the genets in the branches representing the female gametes. The male parents producing the conidia were detected within the same local population as the female parents in 27% of the fertilization events and originated either from the same branch or from different trees located at 0.5–36 m away from the female parents. In 33% of the fertilization events, conidia originated from three male parents that were not found within the local population sampled. These parents could be anywhere inside or outside the sampled area. For the remaining fertilization events, we could not rule out the ascospores or the conidia as fertilizing propagules. No strong evidence for fertilization by recombinant propagules (ascospores) was detected in this study. The pyrophilous insect species associated with conidia of D. loculata are suggested to be essential vectors for the realization of the sexual cycle of this fungal species. By feeding on the conidia and flying between nearby trees inhabiting wood decay mycelia, these insects allow the transfer of conidia and therefore the opposite mating types to meet within a localized burned forest site.
A new approach to detecting mixed families
Authors: Vines Timothy H. , Barton Nicholas H.
Published: June 2003

There are several analyses in evolutionary ecology which assume that a family of offspring has come from only two parents. Here, we present a simple test for detecting when a batch involves two or more subfamilies. It is based on the fact that the mixing of families generates associations amongst unlinked marker loci. We also present simulations illustrating the power of our method for varying numbers of loci, alleles per locus and genotyped individuals.
From connectivity to isolation: genetic consequences of population fragmentation in capercaillie across Europe
Authors: Segelbacher G. , Höglund J. , Storch I.
Published: June 2003

The capercaillie inhabits a continuous range in large parts of the Palearctic boreal forest, but is patchily distributed in temperate Europe. An ongoing population decline, largely related to human land use changes, has been most pronounced in central and western Europe, where some local populations have become extinct. In this study, we document the genetic differentiation of capercaillie populations at different stages along a gradient of spatial structuring from high connectivity (continuous range in the boreal forest) to a metapopulation systems (Alps) and recent (central Europe) and historic (Pyrenees) isolation. Four hundred and sixty individuals from 14 sample sites were genotyped at 10 polymorphic microsatellite loci to assess genetic structure and variation of capercaillie populations across its European range. As expected, differentiation was least pronounced within the continuous range in the boreal forest. Within the metapopulation system of the Alps, differentiation was less than among the isolated populations of central Europe (Black Forest, Fichtelgebirge, Thuringia, Vosges). In the long‐isolated population of the Pyrenees, and the recently isolated populations of central Europe, genetic diversity was significantly reduced compared with the Alps and boreal forest. Our results agree with the concept of a gradual increase in genetic differentiation from connectivity to isolation, and from recent to historic isolation. Anthropogenic habitat deterioration and fragmentation thus not only leads to range contractions and extinctions, but may also have significant genetic and evolutionary consequences for surviving populations. To maintain high levels of genetic variation in species in fragmented habitats, conservation should aim at securing connectivity between spatially distinct populations.
A new mutation, ataxia and male sterility (ams), of autoimmune‐prone MRL/lpr mouse is not linked to lpr gene but associated with reduction of spleen size and alteration of lymphocyte subpopulations
Authors: Pineda Liliam L. , Nakano Akinobu , Iijima Masaaki , Wada Masahiro , Yamasaki Yoji , Harada Takayuki
Published: June 2003

We describe changes in the immune system of the newly established mutant line, ataxia and male sterility (AMS) mouse, and that the putative ams mutation is independent of lpr but seemed to affect lymphoproliferation in its mother strain, MRL/lpr. The mean weights of the spleen and lymph nodes of ams‐lpr double‐homozygous mouse were reduced compared with lpr single‐homozygous mouse. Comparison between ams single‐homozygous and control mice revealed 45–50% reduction of the spleen weight in the former for which reduction of the number of nucleated cells contributed greatly. In the lymphocyte/monocyte fraction of the spleen, there were significant changes in the proportion of lymphocyte subpopulations, with a reduction of B cells, an increase in CD4 and CD8 T cells, and a decrease in the CD4 : CD8 ratio. In vitro response of splenocytes to concanavalin A showed inconspicuous dose‐ and time‐dependent responses in ams homozygous spleen, suggesting functional alteration of the immunological response. Our results indicate that ams mutation affects the immune system in addition to its two other major effects on the central nervous system and male reproductive system.
Prostatic stromal sarcoma: Case report and review of the literature
Authors: Osaki Mari , Osaki Mitsuhiko , Takahashi Chihiro , Miyagawa Tetsuo , Adachi Hironobu , Ito Hisao
Published: June 2003

We report a case of a 65‐year‐old man with rare prostatic stromal sarcoma in which suprapubital radical prostatectomy was performed, but neither chemotherapy nor radiation therapy were administered before or after the operation. The well‐circumscribed tumor, measuring 5 cm in diameter, showed a homogeneous white grayish cut surface with a hard consistency. Histopathologically, the tumor consisted mainly of medium‐sized rounded cells with a sarcomatous and epithelioid appearance intermingled with collagen fiber. Hyalinized foci were also noted in the tumor. Immunohistochemistry revealed that the tumor cells were diffusely positive for vimentin and focally positive for progesterone receptor and CD34, but not for EMA, cytokeratin or estrogen receptor. No recurrence or distant metastasis of the tumor has occurred in 8 years of follow up. The tumor was diagnosed as prostatic stromal sarcoma (PSS) showing epithelioid differentiation and of a progesterone‐dependent nature. Possible favorable nature of the PSS might be expected after complete resection.
Neighbourhood‐scale diversity, composition and root crowding do not alter competition during drought in a native grassland
Authors: Cahill James F.
Published: June 2003

The diversity‐invasion resistance theory argues that increased diversity results in increased competitive suppression of establishing plants. Although there is support for the pattern of decreased invasion with increased diversity, empirical demonstrations of increased competition are limited. An experiment was conducted during a severe drought in a native grassland community. The drought resulted in minimal shading among neighbours, and in contrast to prior studies, competition here was exclusively belowground. Neither diversity nor community composition influenced root crowding or competition. It appears that when competition is belowground, it is independent of diversity, likely because of fundamental differences in the mechanisms of above‐ and belowground competition. This suggests that even at the neighbourhood scale, there is no inherently negative relationship between competition and diversity, and lends support to alternative theories which suggest factors of than diversity may more strongly influence community invasibility.
The bacterial ecology of a plague‐like disease affecting the Caribbean coral Montastrea annularis
Authors: Pantos Olga , Cooney Rory P. , Le Tissier Martin D. A. , Barer Michael R. , O'Donnell Anthony G. , Bythell John C.
Published: June 2003

The bacterial communities associated with the Caribbean coral Montastrea annularis showing tissue lesions indicative of a White Plague (WP)‐like disease were investigated. Two molecular screening techniques using bacterial 16S rDNA genes were used and demonstrated distinct differences between the bacterial communities of diseased and non‐diseased coral tissues, and also in relation to the proximity of tissue lesions on diseased corals. Differences between non‐diseased corals and the apparently healthy tissues remote from the tissue lesion in affected corals indicates a ‘whole coral’ response to a relatively small area of infection with a perturbation in the normal microbial flora occurring prior to the onset of visible signs of disease. These whole organism changes in the microbial flora may serve as a bioindicator of environmental stress and disease. There were striking similarities between the 16S rDNA sequence composition associated with the WP‐like disease studied here and that previously reported in association with black band disease (BBD) in coral. Similarities included the presence of a potential pathogen, an α‐proteobacterium identified as the causal agent of juvenile oyster disease (JOD). The WP‐like disease studied here is apparently different to WP Type ii because the bacterial species previously identified as the causal agent of WP Type ii was not detected, although the symptoms of the two diseases are similar.
Species composition and antimicrobial resistance genes of Enterococcus spp., isolated from integrated and traditional fish farms in Thailand
Authors: Petersen Andreas , Dalsgaard Anders
Published: June 2003

Integrated fish farming uses the manure from animal husbandry as fertilisers in the fish ponds. A total of 410 enterococcal isolates, from integrated and traditional fish farms in Thailand, were collected to assess whether the input of manure from chickens receiving feed containing growth promoters and antimicrobial treatments influenced the species composition and the bacterial antimicrobial resistance in the fish pond environment. Enterococcus faecium and E. faecalis were the predominate species isolated from the integrated farms, whereas E. casseliflavus and E. mundtii isolates were most prevalent in traditional farms. Enterococcus faecalis and E. faecium demonstrated the highest prevalence of resistance, whereas E. mundtii isolates were susceptible to all antimicrobials tested. All the enterococci species isolated from the integrated farms, generally demonstrated higher resistance phenotypes to the tested antimicrobials compared with the same species from traditional farms. The erm(B) and tet(M) genes, associated with resistance to erythromycin and tetracycline, respectively, were found in 87% of the erythromycin‐resistant and 95% of the oxytetracycline‐resistant enterococci isolates respectively. These results suggest that the species composition and antimicrobial resistance of enterococci in tropical aquatic environments are influenced by faecal and antimicrobial pollution.
Headache in Schoolchildren: Agreement Between Different Sources of Information
Authors: Laurell K , Larsson B , Eeg-Olofsson O
Published: June 2003

The level of agreement between different sources of information, i.e. questionnaires, interviews and diaries, was evaluated in a sample of 129 schoolchildren, 69 girls and 60 boys, ranging in age from 7 to 17 years. Headache diagnoses and headache features showed high agreement between questionnaires and subsequent interviews. The concordance between questionnaires and interviews for headache diagnoses increased, and the number of unclassified headaches decreased, when the International Headache Society (IHS) duration criterion was excluded. When comparing headache frequency reported in questionnaires and interviews with diary recordings, the agreement was low and the frequency higher in the diaries. Overall, the agreement between questionnaires, interviews and diaries was not related to age or gender. The questionnaire may serve as a valid source of information in studies of headache in schoolchildren. Prospective recordings in diaries provide additional information, in particular of low-intensity headache. In children, the IHS duration criterion should be modified or excluded.
Migraine Headache Disability and Health-Related Quality-of-life: A Population-Based Case-Control Study from England
Authors: Lipton RB , Liberman JN , Kolodner KB , Bigal ME , Dowson A , Stewart WF
Published: June 2003

The aims of this study were: (i) to compare health-related quality of life (HRQoL) as measured by the Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) in a population sample of migraine headache sufferers and controls without migraine; (ii) to assess the relationship of HRQoL and work-related disability attributed to headache in a population sample. The study was conducted in two phases. First, a population-based, telephone interview survey of 5769 residents of greater London, England was conducted to identify individuals with migraine headache (cases) and controls without migraine. In the second stage, in-person interviews were conducted in a matched sample of 200 migraine cases and 200 controls selected from survey respondents. At the beginning of the in-person interview, participants were asked to complete the SF-36. In addition, a work-related disability score based on the telephone interview was defined as the number of lost work days or days when usual activity was reduced by 50% or more over the previous year. The disability score was trichotomized as mild ( n = 98), moderate ( n = 49), and severe disability ( n = 49). Compared with controls, individuals with migraine headache scored significantly lower in eight of the nine domains of the SF-36 as well as in the overall Physical Component Summary (PCS) score and Mental Component Summary (MCS) score. Further, among migraine sufferers, each of the disability groups scored significantly lower in seven of the nine domains and in the summary scales. Scores showed greater reductions in HRQoL for the moderate and severe disability groups vs. the mild disability group in five of nine scales and in the Total Physical Summary score. We conclude that, in a population-based sample of migraine headache sufferers, individuals with migraine headache have lower HRQoL scores compared with controls. Moreover, among individuals with migraine headache, work-related disability is associated with lower HRQoL scores. Specifically, individuals classified with moderate to severe work-related disability had lower HRQoL scores than those classified with low disability.
Eletriptan for the Treatment of Migraine in Patients with Previous Poor Response or Tolerance to Oral Sumatriptan
Authors: Färkkilä M , Olesen J , Dahlöf C , Stovner LJ , ter Bruggen JP , Rasmussen S , Muirhead N , Sikes C
Published: June 2003

To determine the tolerability and efficacy of eletriptan in patients who had discontinued oral sumatriptan due to lack of efficacy or intolerable adverse events (AEs) during previous clinical treatment (not a controlled trial). Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel group, placebo-controlled multicentre study, patients with and without aura ( n = 446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n = 171) or placebo ( n = 87) for treatment of up to three migraine attacks. Two-hour headache response, based on first-dose, first-attack data, was 59% for eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo ( P < 0.0001 for both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was rapid, with 1-h headache response rates significantly superior for E40 and E80 vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly superior to placebo, based on first-dose, first-attack data, for 2-h pain-free response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated significant consistency of response, with headache relief rates at 2 h on at least two of three attacks in 66% and 72% vs. 15% on placebo ( P < 0.001). AEs were mild to moderate in severity and dose related. The most commonly reported AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce an effective response in patients who had previously discontinued treatment with sumatriptan due to lack of efficacy or side-effects.
The chemokine receptor CCR5 is not a necessary inflammatory mediator in kainic acid‐induced hippocampal injury: evidence for a compensatory effect by increased CCR2 and CCR3
Authors: Chen Zhiguo , Yu Shuo , Bakhiet Moiz , Winblad Bengt , Zhu Jie
Published: June 2003

Chemokines and their receptors have been strongly implicated in the inflammatory process. However, their roles in excitotoxic brain injury are largely unknown. In this study we used C‐C chemokine receptor 5 (CCR5) knockout (KO) mice to investigate the role of CCR5 in neurodegeneration induced by intranasal administration of the excitotoxin kainic acid (KA). Although KA treatment resulted in an increased CCR5 mRNA level in the hippocampi of wild‐type mice, a CCR5 deficiency in KO mice did not affect either the clinical and pathological changes in vivo or the neuronal susceptibilities to KA insult in vitro. KA treatment stimulated mRNA expression of the monocyte chemoattractant protein‐2 (MCP‐2) in both the wild‐type and KO mice. KA treatment did not affect mRNA levels for the macrophage inflammatory protein‐1α (MIP‐1α) or the regulated upon activation normal T cells expressed and secreted protein (RANTES) in either wild‐type or CCR5 KO mice. CCR2 mRNA expression was undetectable in the hippocampi of wild‐type mice regardless of KA treatment. In contrast, CCR5 KO mice showed CCR2 mRNA expression that was remarkably increased after KA treatment. KA treatment did not affect CCR3 mRNA expression in the wild‐type mice, whereas KO mice showed both a higher basal level of CCR3 mRNA expression as well as a strong upregulation following KA treatment. These results indicate that CCR5 is not a necessary inflammatory mediator in KA induced neurodegeneration. The roles of CCR5 in excitotoxic injury in CCR5 deficient mice are compensated by increased CCR2 and CCR3 expression, which share the common MCP‐2 ligand with CCR5.
l‐DOPA supply to the neuro retina activates dopaminergic communication at the early stages of embryonic development
Authors: Kubrusly Regina C. C. , Guimarães Marília Zaluar P. , Vieira Ana Paula B. , Hokoç Jan N. , Casarini Dulce E. , De Mello Maria C. F. , De Mello Fernando G.
Published: June 2003

DOPA decarboxylase (DDC; aromatic‐l‐amino acid decarboxylase; EC 4.1.1.28) is absent in retinas from 6‐day‐old chicken embryos (E6) but is expressed in retina of E8 embryos, in the presumptive outer plexiform layer. Thereafter, DDC appears in cell bodies of presumptive amacrine cells. The dopamine (DA) content of E9/10 and E15/16 retinas, pre‐incubated with l‐DOPA for 1 h, increased 250‐ and 600‐fold, respectively, showing that DDC is active since early in development. Intercellular communication, measured by endogenous cyclic AMP accumulation, was observed when retinas from E9/10 to E15/16 were pre‐incubated for 1 h with 1 mm l‐DOPA, washed and followed by incubation in the presence of 0.5 mm 3‐isobutyl‐1‐methylxanthine, a phosphodiesterase inhibitor. Cyclic AMP accumulation was prevented when pre‐incubation with l‐DOPA was carried out in the presence of carbidopa. Moreover, the accumulation of cyclic AMP was inhibited by SCH 23390 (2 µm). The incubation of retinas in medium previously conditioned by retina‐pigmented epithelium (RPE) also increased its cyclic AMP content with the characteristics described for l‐DOPA. Our results show that dopaminergic communication takes place in the embryonic retina, before tyrosine hydroxylase expression, provided l‐DOPA is supplied to the tissue. It also shows that RPE is a potential source of l‐DOPA early in development.
Regulation of ania‐6 splice variants by distinct signaling pathways in striatal neurons
Authors: Sgambato Véronique , Minassian Raia , Nairn Angus C. , Hyman Steven E.
Published: June 2003

The striatum is a brain region involved in motor control and in diverse forms of implicit memory. It is also involved in the pathogenesis of many significant human disorders, including drug addiction, that are thought to involve adaptive changes in gene expression. We have previously shown that the cyclin L, ania‐6, is expressed as at least two splice forms, which are differentially regulated in striatal neurons by different neurotransmitters. Here, we report that ania‐6 transcription is mostly regulated via cAMP response element binding protein (CREB), but that signaling pathways that converge on CREB at the transcriptional level produce different effects on splicing and neuronal gene expression. Glutamate induced a long ania‐6 mRNA that encodes a truncated form of the cyclin. This effect depended on the activation of NMDA receptors but was independent of both calcium/calmodulin‐dependent protein kinases (CaMK) and extracellular regulated kinase (ERK). Forskolin or brain‐derived neurotropic factor (BDNF) induced a short ania‐6 mRNA, that encodes the full‐length cyclin, and this induction depended on ERK. However, KCl‐mediated induction of ania‐6 short mRNA, which required activation of L‐type calcium channels, was independent of ERK but depended on CaMK. These data suggest that different neuronal signals can differentially regulate splicing and that different intracellular pathways can be recruited to yield a given splice variant.
Pathology and Pathways of Alzheimer's Disease with an Update on New Developments in Treatment
Authors: DeKosky Steven T.
Published: June 2003

As our understanding of the complex pathology of Alzheimer's disease improves, more targets for therapy emerge. These include the actions of beta amyloid, the inflammatory cascade, pathobiology of tau proteins' conversion to neurofibrillary tangles, oxidative neuronal damage, and neurotransmitter depletion. Many agents now under investigation target the early stages of the disease process, aiming to prevent or slow the development of symptoms. This article reviews the current understanding of the course and pathology of Alzheimer's disease as it relates to emerging therapies, then summarizes some promising current research directions in primary prevention, secondary prevention, and treatment.
Calculation of crystal and molecular structures of the temperature and pressure polymorphs of para-dichlorobenzene p-C6H4Cl2
Authors: Thiéry M-M. , Rérat C.
Published: June 2003

Crystal and molecular structures of the polymorphic para-dichlorobenzene p-C6H4Cl2 (p-DCB) were investigated by molecular packing analysis with a computed dynamical model. This model includes anisotropic atomic repulsive interactions, molecular deformations, and thermal motions. Several crystalline structures with triclinic P1̄, monoclinic P21/a (and P21/c) symmetry have been found by the calculation. Calculated crystal and molecular parameters agree with data of the three phases β, α, and γ determined by x-ray diffraction between 300–100 K at ambient pressure. At room temperature various crystal structures with orthorhombic Pbca and Abma symmetry calculated in the pressure range of a fourth pressure-induced phase δ are compared with the experimental structure δ0 proposed for this phase. Among them the orthorhombic Abma structure named δs has the lowest energy and enthalpy. It is suggested as a possible structure for the high pressure phase δ.
The central role of excluded volume in the production of anisotropic stress in deformed polymer melts
Authors: Bower A. F. , Weiner J. H.
Published: June 2003

Nonequilibrium molecular dynamics computations are used to calculate the stress relaxation in an idealized “pearl necklace” polymer melt. The covalent bonds in the melt are approximated by stiff linear springs with potential ub(r), while nonbonded atoms interact through a Lennard-Jones potential unb(r), which includes both a short-range repulsive portion, and a long-range attractive tail. The simulations are used to calculate the relaxation of difference stress t11−(t22+t33)/2 in the melt following a constant volume extension in the x1 direction. Results show that the dominant contribution to the difference stress arises from excluded volume interactions, through the repulsive portion of the Lennard-Jones potential, while the attractive tail gives rise to only a small portion of the difference stress. In contrast, attractive nonbonded interactions provide a dominant contribution to the mean stress. This behavior occurs because the difference stress is generated by deformation induced anisotropy in the orientation of nonbonded interactions acting on a representative atom in the melt. The anisotropy is localized to a small region surrounding the atom. The anisotropy in the orientation of these nonbonded pairs is generated by steric shielding: the deformation tends to orient the chain bonds parallel to the stretch direction, and so orients nonbonded pairs transverse to the stretch direction.
The evolution of the monoelectron dihydrogen bond H⋯e⋯H in the symmetric and asymmetric cluster anions (FH)n{e}(HF)m
Authors: Hao Xi-Yun , Li Zhi-Ru , Wu Di , Li Ze-Sheng , Sun Chia-Chung
Published: June 2003

Using the aug-cc-pVDZ basis set supplemented with diffuse bond functions (BF), the evolution of the monoelectron dihydrogen bond H⋯e⋯H in the symmetric (n=m=2–5) and asymmetric (n,m:3,1;3,2;4,2;4,3) cluster anions (FH)n{e}(HF)m have been studied. When n=m=3, 4, 5, and n, m: 3, 2 the H⋯e⋯H bond evolves into the FH–e–HF monoelectron bimolecular bond. While in some asymmetric cluster anions (n,m:4,2;4,3) the FH–e–HF bond changes to H–e–HF bond, and some bond rearrangements occur in the larger subunit (HF)4 at the same time. This evolution shows a size effect of the subunits on the structure and the bond for the molecular cluster anions.
Electronic structures, vibrational spectra, and revised assignment of aniline and its radical cation: Theoretical study
Authors: Wojciechowski Piotr M. , Zierkiewicz Wiktor , Michalska Danuta , Hobza Pavel
Published: June 2003

Comprehensive studies of the molecular and electronic structures, vibrational frequencies, and infrared and Raman intensities of the aniline radical cation, C6H5NH2+ have been performed by using the unrestricted density functional (UB3LYP) and second-order Møller–Plesset (UMP2) methods with the extended 6-311++G(df,pd) basis set. For comparison, analogous calculations were carried out for the closed-shell neutral aniline. The studies provided detailed insight into the bonding changes that take place in aniline upon ionization. The natural bond orbital (NBO) analysis has revealed that the pπ-radical conjugative interactions are of prime importance in stabilizing the planar, quinoid-type structure of the aniline radical cation. It is shown that the natural charges calculated for aniline are consistent with the chemical properties of this molecule (an ortho- and para-directing power of the NH2 group in electrophilic substitutions), whereas Mulliken charges are not reliable. The theoretical vibrational frequencies of aniline, calculated by the B3LYP method, show excellent agreement with the available experimental data. In contrast, the MP2 method is deficient in predicting the frequencies of several modes in aniline, despite the use of the extended basis set in calculations. The frequencies of aniline radical cation, calculated at the UB3LYP/6-311++G(df,pd) level, are in very good agreement with the recently reported experimental data from zero kinetic energy photoelectron and infrared depletion spectroscopic studies. The clear- cut assignment of the IR and Raman spectra of the investigated molecules has been made on the basis of the calculated potential energy distributions. Several bands in the spectra have been reassigned. It is shown that ionization of aniline can be easily identified by the appearance of the very strong band at about 1490 cm−1, in the Raman spectrum. The redshift of the N–H stretching frequencies and the blueshift of the C–H stretching frequencies are observed in aniline, upon ionization. As revealed by NBO analysis, the frequency shifts can be correlated with the increase of electron density (ED) on the antibonding orbitals (σNH*) and decrease of ED on σCH*, respectively. These effects are associated with a weakening of N–H bonds and strengthening of C–H bonds in the aniline radical cation. The simulated theoretical Raman and infrared spectra of aniline and its radical cation, reported in this work, can be used in further spectroscopic studies of their van der Waals clusters and hydrogen bonded complexes.
Dynamics of squeeze-out: Theory and experiments
Authors: Zilberman S. , Becker T. , Mugele F. , Persson B. N. J. , Nitzan A.
Published: June 2003

We consider the dynamics of squeeze-out of a molecularly thin confined two-dimensional (2D) liquidlike layer. The squeeze-out is described by a generalized 2D Navier–Stokes equation which is solved exactly for the limiting case where the squeeze-out nucleates at the center of the contact area, and where the (perpendicular) three-dimensional pressure profile is Hertzian. We also present numerical results for the case where the nucleation is off-center. The theoretical results are in good agreement with recent experimental data by two of us for octamethylcyclotetrasiloxane. In light of our theoretical model calculations, we also discuss the spatially resolved diffusion experiments of Mukhopadhyay et al. [Phys. Rev. Lett. 89, 136103 (2002)]. Here, we obtain a puzzling disagreement between theory and experiment which requires more investigation.
Degradation of functionalized alkanethiolate monolayers by 0–18 eV electrons
Authors: Huels Michael A. , Dugal Pierre-Cyrille , Sanche Léon
Published: June 2003

Electron stimulated desorption of neutral molecular fragments is used to study degradation of ordered organic thin films under low-energy (0–18 eV) electron impact, and total electron doses ranging between 180–550 μC/cm2. Different saturated linear thiols HS(CH2)nX (n=2 or 15, and X=CH3 or COOH) are adsorbed from solution onto a gold surface to produce a self-assembled monolayer (SAM). Here, we present yield function measurements for electron stimulated desorption of moities such as H2, CH3, CH3CH2, CH3CH2CH2, CO, and CO2 from such thin chemisorbed films. For CH3-terminated SAMs, neutral fragment desorption thresholds lie between 5–7 eV, whereas for COOH-terminated SAMs, desorption thresholds as low as 0.2 and 3–5 eV are observed. The results suggest that the incident electrons interact with functional groups localized at the film–vacuum interface, which then leads to predominantly methyl group C–H, and C–COOH bond cleavage. In addition to nonresonant degradation mechanisms, which vary monotonically from threshold with increasing incident electron energy, structures in the neutral fragment desorption yield functions are related to resonant electron attachment. Particularly for Au–S(CH2)15COOH monolayers, this mechanism leads to a desorption peak of CO fragments at incident electron energies near 1.0 eV.
Spectroscopy and dynamics of excited states in maleimide and N-methyl maleimide: Ionic projection and ab initio calculations
Authors: ter Steege D. H. A. , Buma W. J.
Published: June 2003

The state that is responsible for the strong one-photon absorption around 200 nm in the vapor absorption spectrum of maleimide and N-methyl maleimide has been investigated using excited-state photoelectron spectroscopy in combination with ab initio calculations. The projection of the wave function of the excited state on the ionic manifold done in this way reveals multiple, vibrationally resolved, ionization pathways to ground- and excited states of the radical cation, which provide direct evidence for electronic couplings with other, lower-lying states. From a comparison of the experimental intensity distribution over the ionic vibrational states with ab initio calculated Franck–Condon factors, we are able to elucidate the role of the various electronically excited states in the ionization process. The experiments also provide the first determination of adiabatic ionization energies in the two molecules. For maleimide values of 10.330 and 10.903 eV are found for D0 and D1, respectively; for N-methyl maleimide D0 is found at 9.897 or, in an alternative interpretation of the spectrum, at 9.676 eV. Calculations and experiment demonstrate that in this molecule the ground ionic state changes its character with respect to maleimide from a lone pair to a π orbital ionization.
Revisiting the stationary points on the potential energy surface of tetramethylene at the MR-AQCC level using analytic gradients
Authors: Ventura Elizete , Dallos Michal , Lischka Hans
Published: June 2003

The stationary points on the potential energy surface (PES) of tetramethylene have been investigated using highly correlated multireference methods and extended basis sets. Full geometry optimization using analytic gradients as well as systematic scans of the PES employing different basis sets show that all minima and most of the saddle points found at the lower computational level (mostly CASSCF) cease to exist. Finally, only the G2 (gauche cyclization with conrotatory double CH2 twist) and the CT (cis–trans isomerization) saddle points have been confirmed. Activation and reaction enthalpies have been computed and are within 1–2 kcal/mol in agreement with experimental results.
Interaction of rare-gas-containing molecules with nitrogen: Matrix-isolation and ab initio study of HArF⋯N2, HKrF⋯N2, and HKrCl⋯N2 complexes
Authors: Lignell Antti , Khriachtchev Leonid , Pettersson Mika , Räsänen Markku
Published: June 2003

The complexes of HArF, HKrF, and HKrCl with nitrogen molecules have been studied computationally and experimentally. With the help of computations the experimental data can be interpreted as showing the presence of two complex configurations, one linear and one bent. Vibrational properties of the studied molecules are very sensitive to the intermolecular interactions and complexation induces an exceptionally large blueshift (>100 cm−1 for HKrCl) to the H–Ar and H–Kr stretching frequency, especially for the linear configurations. The interaction energies without zero-point energy correction are between 400 and 800 cm−1. According to the energy decomposition scheme, the electrostatic forces provide the most important interaction in the linear complex configurations. For the bent complexes, electrostatic and dispersion forces are competing as a leading attractive interaction.
Role of dynamic trapping in H2 dissociation and reflection on Pd surfaces
Authors: Di Césare M. A. , Busnengo H. F. , Dong W. , Salin A.
Published: June 2003

We present results of classical trajectory calculations on dissociative adsorption and reflection of H2 impinging on a frozen Pd(110) surface. The six-dimensional potential energy surface is obtained by interpolation of density functional theory (DFT) calculations using the corrugation reducing procedure. The comparison with earlier work for H2/Pd(111) shows that DFT calculations predict that the Pd(110) surface, though more open, is less reactive than the Pd(111) one. This lower reactivity is associated with a more prominent role of dynamic trapping, at low energies, and with the fact that trapping may end up in reflection as well as in dissociation.