bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pain Clinic
Authors: Rounsefell Bruce
Published: July 2007

Abstract: The multi‐disciplinary approach to the management of chronic, intractable pain problems is now a well established concept. Processes of assessment and management by a Pain Clinic are outlined, with discussion of treatment and prescribing regimes.
Experimental Models of Opiate Tolerance and Dependence
Authors: Johnson Stephen
Published: July 2007

Abstract: Since observations in whole animals provide only limited information on the mechanisms underlying tolerance and dependence, less complex isolated tissue, cell culture and single neurone models have been developed, the most widely exploited of which is the guinea pig ileum. Prolonged exposure to morphine leads to tolerance to its acute inhibitory effects. Dependence is indicated by neuronal hyperexcitability when morphine is withdrawn or abruptly displaced from its receptor by naloxone. The mechanism of withdrawal hyperexcitability may be relatively non‐selective since responses of both central and peripheral neurones to a variety of excitants are enhanced. Behavioural and biochemical experiments implicate elevated neuronal calcium and adenylate cyclase in the expression of dependence. However the relationship between these observations and the hyperexcitability of single neurones has not been rigorously examined. Moreover the relevance of an analysis of tolerance and physical dependence in experimental models to opioid reward mechanisms is uncertain. Although recent evidence suggests the importance of the ventral tegmental area in the rewarding actions of opiates, the biochemical and electrophysiological effects of exogenous opiates and of endogenous opioids on these neurones remain largely unexplored.
Cortical processing and perceived timing
Authors: Arnold Derek H , Wilcock Paul
Published: July 2007

As of yet, it is unclear how we determine relative perceived timing. One controversial suggestion is that timing perception might be related to when analyses are
completed
in the cortex of the brain. An alternate proposal suggests that perceived timing is instead related to the point in time at which cortical analyses
commence
. Accordingly, timing illusions should not occur owing to cortical analyses, but they could occur if there were differential delays between signals reaching cortex. Resolution of this controversy therefore requires that the contributions of cortical processing be isolated from the influence of subcortical activity. Here, we have done this by using binocular disparity changes, which are known to be detected via analyses that originate in cortex. We find that observers require longer stimulus exposures to detect small, relative to larger, disparity changes; observers are slower to react to smaller disparity changes and observers misperceive smaller disparity changes as being perceptually delayed. Interestingly, disparity magnitude influenced perceived timing more dramatically than it did stimulus change detection. Our data therefore suggest that perceived timing is both influenced by cortical processing and is shaped by sensory analyses subsequent to those that are minimally necessary for stimulus change perception.
Flight muscle myofibrillogenesis in the pupal stage ofDrosophilaas examined by X-ray microdiffraction and conventional diffraction
Authors: Iwamoto Hiroyuki , Inoue Katsuaki , Matsuo Tatsuhito , Yagi Naoto
Published: July 2007

In the asynchronous flight muscles of higher insects, the lattice planes of contractile filaments are strictly preserved along the length of each myofibril, making the myofibril a millimetre-long giant single multiprotein crystal. To examine how such highly ordered structures are formed, we recorded X-ray diffraction patterns of the developing flight muscles ofDrosophilapupae at various developmental stages. To evaluate the extent of long-range myofilament lattice order, end-on myofibrillar microdiffraction patterns were recorded from isolated quick-frozen dorsal longitudinal flight muscle fibres. In addition, conventional whole-thorax diffraction patterns were recorded from live pupae to assess the extent of development of flight musculature. Weak hexagonal fluctuations of scattering intensity were observed in the end-on patterns as early as approximately 15 h after myoblast fusion, and in the following 30 h, clear hexagonally arranged reflection spots became a common feature. The result suggests that the framework of the giant single-crystal structure is established in an early phase of myofibrillogenesis. Combined with published electron microscopy results, a myofibril in fused asynchronous flight muscle fibres is likely to start as a framework with fixed lattice plane orientations and fixed sarcomere numbers, to which constituent proteins are added afterwards without altering this basic configuration.
Identification and characterization of a novel spliced form of the meq transcript in lymphoblastoid cell lines derived from Marek's disease tumours
Authors: Okada Tsukasa , Takagi Michihiro , Murata Shiro , Onuma Misao , Ohashi Kazuhiko
Published: July 2007

In tumour cell lines established from Marek's disease (MD) lymphomas L-meqis consistently expressed. It contains a 180 bp insertion encoding additional copies of the proline-rich repeat in themeqopen reading frame and its product may contribute to the maintenance of MD virus (MDV) latency. In this study, we identified a novel spliced form of themeqtranscript in MD-derived lymphoblastoid cell lines and in MDV-infected cells. This transcript, termed Δmeq, encodes an N-terminal 98 aa of the Meq protein and lacks part of the basic leucine zipper (bZIP) and transactivation domains. In MD cell lines, transcription of L-meqwas significantly downregulated, while that of the Δmeqtranscript was upregulated during apoptosis. These observations were also confirmed at the protein expression level. Reporter assays usingmeq- andinterleukin-2(IL-2)-promoter-driven luciferase vectors revealed that ΔMeq suppressed transactivation by L-Meq or Meq in a dose-dependent manner. Immunoprecipitation confirmed that ΔMeq was associated with L-Meq or Meq physically. These results suggest that ΔMeq could be involved in apoptosis in MD cell lines as it works as a negative regulator of L-Meq and Meq by direct interaction.
Apoptosis is induced in the haemolymph and fat body of Spodoptera exigua larvae upon oral inoculation with Spodoptera litura nucleopolyhedrovirus
Authors: Feng Guozhong , Yu Qian , Hu Chaoyang , Wang Yanjie , Yuan Guangming , Chen Qijin , Yang Kai , Pang Yi
Published: July 2007

Spodoptera exigua multinucleopolyhedrovirus (SeMNPV) and Spodoptera litura nucleopolyhedrovirus (SpltNPV) are genetically similar, but the larvae of S. exigua are not susceptible to SpltNPV. The aim of this study was to identify whether any process was inhibiting SpltNPV infection at some point. S. exigua larvae infected with a high concentration of wild-type SpltNPV by oral inoculation produced a fatal infection in second- or third-instar S. exigua, but the dead larvae did not undergo liquefaction; in contrast, fourth-instar infected larvae remained healthy. RT-PCR analysis of total RNA from infected second-instar larvae targeting immediate-early (ie-0), early (dnapol), late (chit) and very late (polh) genes suggested that SpltNPV initiated infection in the non-susceptible hosts. Total DNA extracted from the haemocytes of infected larvae showed DNA ladders characteristic of apoptosis. Sections of tissue from infected third-instar larvae of S. exigua at 96 h post-inoculation, stained with haematoxylin and eosin, revealed a highly disrupted morphology in the fat body. Apoptosis in fat body tissue was detected using terminal deoxynucleotidyltransferase-mediated fluorescein–dUTP nick end labelling (TUNEL) assays. In situ hybridization revealed the presence of viral DNA within the TUNEL-positive area, indicating viral infection in this tissue. These results suggest that apoptosis limits viral propagation by reducing the number of SpltNPV-infected haemocytes and fat body cells and inhibits disseminated viral infection.
Control of ruminant morbillivirus replication by small interfering RNA
Authors: Servan de Almeida Renata , Keita Djénéba , Libeau Geneviève , Albina Emmanuel
Published: July 2007

Peste-des-petits-ruminants virus (PPRV) and rinderpest virus (RPV) are two morbilliviruses of economic relevance in African and Asian countries. Although efficient vaccines are available for both diseases, they cannot protect the animals before 14 days post-vaccination. In emergencies, it would be desirable to have efficient therapeutics for virus control. Here, two regions are described in the nucleocapsid genes of PPRV and RPV that can be targeted efficiently by synthetic short interfering RNAs (siRNAs), resulting in a >80 % reduction in virus replication. The effects of siRNAs on the production of viral RNA by real-time quantitative PCR, of viral proteins by flow cytometry and of virus particles by appreciation of the cytopathic effect and virus titration were monitored. The findings of this work highlight the potential for siRNA molecules to be developed as therapeutic agents for the treatment of PPRV and RPV infections.
The cysteine protease inhibitors cystatins inhibit herpes simplex virus type 1-induced apoptosis and virus yield in HEp-2 cells
Authors: Peri Piritta , Hukkanen Veijo , Nuutila Kristiina , Saukko Pekka , Abrahamson Magnus , Vuorinen Tytti
Published: July 2007

The role of cystatins in herpes simplex virus (HSV)-induced apoptosis and viral replication has been studied. Human epithelial (HEp-2) cells infected with wild-type HSV-1 (F), with a deletion virus lacking the anti-apoptotic gene Us3 (R7041) or with a deletion virus lacking the anti-apoptotic genes Us3 and ICP4 (d120) were treated with cystatin A, C or D. Cells and culture media were studied at different time points for replicating HSV-1 and for apoptosis. Cystatins C and D inhibited the yield of replicative HSV-1 significantly in HEp-2 cells. In addition, cystatin D inhibited R7041 and d120 virus-induced apoptosis. Moreover, cystatin A inhibited R7041-induced apoptosis. These inhibitory effects of cystatins on virus replication and apoptosis are likely to be separate functions. Cystatin D treatment decreased cellular cathepsin B activity in HSV-1 infection, suggesting that cathepsin B is involved in virus-induced apoptosis.
Heart Failure in Older Adults: A Conversation With Dr Michael Rich
Authors: Ahmed Ali , Rich Michael W.
Published: July 2007

Commencing with this issue, we introduce a new department devoted to the education of the elderly cardiac patient. The column has been formatted as a tear‐out sheet and may be used by the clinician for patient education. Dr. Ahmed invites suggestions of topics of concern to your patients; topic suggestions may be forwarded to Elizabeth Ferretti, Editorial Director (lferretti@lejacq.com).—Nanette K. Wenger, MD, Editor in Chief
Interleukin‐12p40 overexpression promotes interleukin‐12p70 and interleukin‐23 formation but does not affect bacille Calmette–Guérin and Mycobacterium tuberculosis clearance
Authors: Olleros Maria L. , Vesin Dominique , Martinez‐Soria Eduardo , Allenbach Cindy , Tacchini‐Cottier Fabienne , Pache Jean‐Claude , Marchal Gilles , Rahman Jubayer , Fernández Carmen , Izui Shozo , Garcia Irene
Published: July 2007

Interleukin (IL)‐12p40, a subunit of IL‐12p70 and IL‐23, has previously been shown to inhibit IL‐12p70 activity and interferon‐γ (IFN‐γ) production. However, recent evidence has suggested that the role of IL‐12p40 is more complex. To study the contribution of IL‐12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL‐12p40 under the control of a major histocompatibility complex‐II promoter. The IL‐12p40 transgene was expressed during steady state at concentrations of 129 ± 25 ng/ml of serum and 75 ± 13 ng per spleen, while endogenous IL‐12p40 was hardly detectable in control littermates. Bacille Calmette–Guérin (BCG) infection strongly induced the expression of IL‐12p40 transgene in infected organs, and IL‐12p40 monomeric and dimeric forms were identified in spleen of IL‐12p40 tg mice. Excessive production of IL‐12p40 resulted in a 14‐fold increase in IL‐12p70 serum levels in tg mice versus non‐transgenic mice. IL‐23 was also strongly elevated in the serum and spleens of IL‐12p40 tg mice through BCG infection. While IFN‐γ and tumour necrosis factor protein levels were similar in IL‐12p40 tg and non‐transgenic mice, Th2 type immune responses were reduced in IL‐12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL‐12p40 tg and non‐transgenic mice. IL‐12p40 tg mice were as resistant as non‐transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL‐12p40 promotes IL‐12p70 and IL‐23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs.
Direct infection of potato tubers by the root parasiteOrobanche aegyptiaca
Authors: JOEL D M
Published: July 2007

Parasitic plants of the Orobanchaceae are known as obligate root parasites that develop haustoria that connect to roots of various host plants. This article describes, for the first time, a case where the root parasite successfully connected to potato tubers, i.e. to the swollen portion of an underground stem rather than to a root. The rhizosphere ofOrobanche aegyptiacaand of its hostSolanum tuberosum(potato) was carefully examined. In anatomical studies, the adventitious roots were directly connected to potato tubers. Numerous secondary haustoria, which developed along the adventitious roots in close vicinity to the potato tuber, penetrated the tuber epidermis and the perimedullary tuber parenchyma and developed xylem strands that are presumably connected to the minor xylem strands within the tuber cortex. These findings indicate that parasites of the Orobanchaceae that normally attack host roots may also parasitise underground stem tubers.
Early treatment of acute rejections gives favorable long‐term function after renal transplantation in small children
Authors: Qvist Erik , Their Maria , Krogerus Leena , Holmberg Christer , Jalanko Hannu
Published: July 2007

Abstract:  AR is considered as a risk factor for CAN after kidney TX. We combined data on AR with long‐term graft function and histopathology to assess whether early treatment of AR is beneficial for long‐term graft outcome in small children. Seventy‐seven children with a mean age of 4.7 yr were studied. Early AR were diagnosed with FNAB and treated with methylprednisolone already before clinical signs occurred. The children were grouped into three groups (clinical, subclinical, and no AR) and then followed prospectively up to seven yr after TX with measured GFR and core needle biopsies to assess histopathological findings with the CADI score. Early AR, whether clinical or subclinical, did not affect long‐term graft survival (80% with AR vs. 83% without AR, at 10 yr). Late AR, more than one yr after TX, had an inferior graft survival 50% vs. 84% (p = 0.02). GFR declined and the CADI scores increased with time, but there were no significant differences between the three groups. Prompt and early treatment of post‐operative AR gives favorable long‐term graft function compared with children without AR. Late AR is a risk factor for inferior long‐term graft function.
Determination of self‐incompatible genotypes in sweet cherry (Prunus avium L.) accessions and cultivars of the German Fruit Gene Bank and from private collections
Authors: Schuster M. , Flachowsky H. , Köhler D.
Published: July 2007

Sweet cherries are self‐incompatible because of a gametophytic self‐incompatibility system. S alleles in the style and pollen determine the crossing relationships. Knowledge of the S allele constitution of cultivars is very important for cherry growers and breeders, and recently, molecular methods have been developed to distinguish the S alleles in sweet cherries. The S allele genotypes of 149 sweet cherry cultivars and clones, including 126 not previously genotyped, were determined by using PCR analysis. Thirteen different S alleles in 40 combinations were distinguished and nine new incompatibility groups were documented. Two new S alleles were identified in five local sweet cherry processing cultivars from southwestern Germany using the second intron primers. The sequence of these alleles was determined and compared to all known sequences available in the NCBI database. The sequences obtained showed high similarities to the alleles S19 and S22, previously described only in wild cherries, Prunus avium L.
Dynamic analyses of rice blast resistance for the assessment of genetic and environmental effects
Authors: Li Y. B. , Wu C. J. , Jiang G. H. , Wang L. Q. , He Y. Q.
Published: July 2007

A doubled haploid population was employed to characterize the dynamic changes of the genetic components involved in rice blast resistance, including main‐effect quantitative trait loci (QTLs), epistatic QTLs and QTL‐by‐environment interactions. The study was carried out at three different developmental stages of rice, using natural infection tests over 2 years. The number of main‐effect QTLs, epistatic QTLs and their environmental interactions differed across the various measuring stages. One QTL (d12) on chromosome 12 was detected at all stages, whereas most QTLs were active only at one or two stages in the population. These findings suggest that the unstable expression of most QTLs identified for blast resistance was influenced by the developmental status of the plants, epistatic effects between different loci and the environments in which they were grown. These findings demonstrate the complexity of expression of rice blast resistance and have important implications for durable resistance‐breeding and map‐based cloning of quantitative traits.
Spectrum of autoimmune liver diseases in western India
Authors: Amarapurkar Deepak N , Patel Nikhil D
Published: July 2007

Background and Aim:  The prevalence and spectrum of autoimmune liver diseases (AILDs) in India are rarely reported in comparison to the West.

Method:  During a study period of 7 years, all patients with chronic liver diseases (CLDs) were evaluated for the presence of AILDs on the basis of clinical, biochemical, imaging, serological, and histological characteristics.

Results:  Of a total of 1760 CLD patients (38.1% females), 102 patients (5.7%) had an AILD. A total of 75 (11.2%) female patients had an AILD. Among males, 27 (2.4%) had an AILD. The prevalence of AILDs in women increased from 11.2% to 45.7% and in men from 2.4% to 10.3%, after excluding alcohol, hepatitis B virus, and hepatitis C virus as a cause of CLD. Of the AILDs, autoimmune hepatitis (AIH) was present in 79 patients (77.4%), followed in descending order by primary biliary cirrhosis (PBC) in 10 patients (9.8%), PBC/AIH true overlap syndrome in six patients (5.8%), primary sclerosing cholangitis (PSC) in five patients (4.9%), and PBC/AIH switchover syndrome in two patients (1.9%). None had PSC/AIH or PBC/PSC overlap syndrome. Associated known autoimmune diseases were found in 40 (39.2%) patients.

Conclusions:  AILDs are not uncommon in India. They should be suspected in all cases of CLDs, especially in middle‐aged women who do not have problems with alcoholism and who are without viral etiology, as well as in all patients with known autoimmune diseases.
Migrating neuroblasts of the rostral migratory stream are putative targets for the action of nitric oxide
Authors: Gutièrrez‐Mecinas María , Crespo Carlos , Blasco‐Ibáñez José Miguel , Nácher Juan , Varea Emilio , Martínez‐Guijarro Francisco José
Published: July 2007

It has been demonstrated that the gaseous messenger nitric oxide influences cell proliferation and cell migration, and therefore affects adult neurogenesis in mammals. Here, we investigated the putative targets for this action in the rostral migratory stream of the rat. We used immunocytochemical detection of the β1 subunit of the enzyme soluble guanylyl cyclase, which can be activated by nitric oxide. Our results under light and electron microscopy demonstrated that the migrating neuroblasts (type A cells) were β1‐immunopositive. The astrocytes (type B cells), immature precursors (type C cells) and ependymal cells (type E cells) were β1‐immunonegative. The neurochemical characterization of the soluble guanylyl cyclase‐containing cells confirmed these results. In this regard, the β1‐containing cells expressed doublecortin, a protein expressed by type A cells, and did not express glial fibrillary acidic protein, which is a marker for type B cells. Injection of 5‐bromo‐2′‐deoxyuridine 2 h before killing demonstrated that proliferating cells did not contain soluble guanylyl cyclase. Finally, we found that β1‐containing type A cells also expressed the A3 subunit of the cyclic nucleotide‐gated ion channels. Altogether, the present results indicate that nitric oxide may influence adult neurogenesis acting on the migrating neuroblasts of the rostral migratory stream. In these cells, nitric oxide may activate the enzyme soluble guanylyl cyclase, triggering the production of the second messenger cGMP. In turn, cGMP might induce the opening of cyclic nucleotide‐gated ion channels, which are present in these cells.
Human impacts on the species–area relationship in reef fish assemblages
Authors: Tittensor Derek P. , Micheli Fiorenza , Nyström Magnus , Worm Boris
Published: July 2007

The relationship between species richness and area is one of the oldest, most recognized patterns in ecology. Here we provide empirical evidence for strong impacts of fisheries exploitation on the slope of the species–area relationship (SAR). Using comparative field surveys of fish on protected and exploited reefs in three oceans and the Mediterranean Sea, we show that exploitation consistently depresses the slope of the SAR for both power‐law and exponential models. The magnitude of change appears to be proportional to fishing intensity. Results are independent of taxonomic resolution and robust across coral and rocky reefs, sampling protocols and statistical methods. Changes in species richness, relative abundance and patch occupancy all appear to contribute to this pattern. We conclude that exploitation pressure impacts the fundamental scaling of biodiversity as well as the species richness and spatial distribution patterns of reef fish. We propose that species–area curves can be sensitive indicators of community‐level changes in biodiversity, and may be useful in quantifying the human imprint on reef biodiversity, and potentially elsewhere.
Growth–size scaling relationships of woody plant species differ from predictions of the Metabolic Ecology Model
Authors: Russo Sabrina E. , Wiser Susan K. , Coomes David A.
Published: July 2007

The Metabolic Ecology Model predicts that tree diameter (D) growth (dD/dt) scales withD1/3. Using data on diameter growth and height–diameter relationships for 56 and 40 woody species, respectively, from forests throughout New Zealand, we tested one prediction and two assumptions of this model: (i) the exponent of the growth–diameter scaling relationship equals 1/3 and is invariant among species and growth forms, (ii) small and large individuals are invariant in their exponents and (iii) tree height scales withD2/3. We found virtually no support for any prediction or assumption: growth–diameter scaling exponents varied substantially among species and growth forms, correlated positively with species’ maximum height, and shifted significantly with increasing individual size. Tree height did not scale invariantly with diameter. Based on a quantitative test, violation of these assumptions alone could not explain the model's poor fit to our data, possibly reflecting multiple, unsound assumptions, as well as unaccounted‐for variation that should be incorporated.
Rural Development and Embeddedness: The Importance of Human Relations for Industrial Restructuring in Rural Areas
Authors: Fløysand Arnt , Sjøholt Peter
Published: July 2007

This article offers a critical reading of theories on embeddedness emphasised in discussions on restructuring and other changes in rural areas. Despite expanding globalisation, embeddedness is considered a local or regional phenomenon that generally promotes the socioeconomic development of rural areas. We argue that the ways in which different forms of embeddedness affect industrial restructuring in a rural place, and how strongly they do so are not given a priori. In addition, embeddedness may differ in geographical scale. This makes us introduce a social field approach that we argue can handle the challenge of mapping multi‐scale and multicultural forms of embeddedness and its significance for economic performance and local economic development. The empirical part of the article starts by analysing changes in the geographical embeddedness of the industrial environment in the municipality of Stryn, Norway. This is followed by a discussion of the cultural embeddedness of the environment, focusing on untraded assets in the present social field system of the industry. The case study demonstrates that industrial environments in peripheral areas should balance social fields of different untraded assets and scope to promote viable communities.
Hospes: The Wabash Center as a Site of Transformative Hospitality
Authors: Jones Carolyn M.
Published: July 2007

Abstract.  The Wabash Center for Teaching and Learning in Theology and Religion is a place of hospitality and its staff the epitome of the “good host.” This essay explores the meaning of hospitality, including its problematic dimensions, drawing on a number of voices and texts: Jacques Derrida's Of Hospitality; Henri M. Nouwen's Reaching Out: The Three Movements of the Spiritual Life, N. Lynne Westfield's Dear Sisters: A Womanist Practice of Hospitality, Arthur Sutherland's I Was a Stranger: A Christian Theology of Hospitality, and Kathleen Norris's “Hospitality.” Beginning with the claim that hospitality is concerned with power and grace, the essay explores the relationship between hospitality and teaching, and the modes by which the Wabash Center helps teachers both find their identities and heal.
Association of insertion/deletion polymorphism of the angiotensin‐converting enzyme gene with angio‐oedema accompanying chronic urticaria but not chronic urticaria without angio‐oedema or the autologous serum skin test response
Authors: Akcali C , Ozkur M , Erbagci Z , Benlier N , Aynacioglu AS
Published: July 2007

Background  Chronic urticaria is defined as the daily or almost daily occurrence of weals for more than 6 weeks. The underlying pathophysiology is reported to be mast cell activation, with release of mast cell mediators, predominantly histamine. Substance P is a neuropeptide and has the capacity to provoke histamine release from skin mast cells. Angiotensin‐converting enzyme (ACE), widely expressed in skin, is one of the major peptidase for the degradation of substance P. An insertion/deletion polymorphism (I/D) in the ACE gene has been reported to be related to the levels of enzyme.

Objective  An increase in substance P levels due to a polymorphism in ACE gene might be related to the pathology. Thus, we aimed to investigate whether there is an association between ACE I/D polymorphism and chronic ordinary urticaria.

Methods Ninety‐five patients with chronic ordinary urticaria were recruited and divided into two groups according to autologous serum skin test status and accompanying angio‐oedema. One hundred and sixty‐one healthy subjects were enrolled as control group. All participants were genotyped for I/D polymorphism in intron 16 of the ACE gene by polymerase chain reaction.

Results  A statistically significant association was not found between ACE I/D polymorphism and chronic ordinary urticaria. Further analyses of chronic ordinary urticaria patients showed that ACE I/D polymorphism was not associated with autologous serum skin test status of patients. However, the frequencies of II genotype and I allele were statistically significantly higher in chronic ordinary urticaria patients with accompanying angio‐oedema with regard to angio‐oedema‐negative patients (II genotype: 24% vs. 9%, P = 0.0002; I allele: 58% vs. 27%, P = 0.0001) and control group (II genotype: 24% vs. 19%, P = 0.01; I allele: 58% vs. 41%, P = 0.03).

Conclusion  The results of this study suggest no evidence of an association between ACE I/D polymorphism and risk of developing chronic ordinary urticaria. However, it can be a contributing factor to susceptibility of angio‐oedema in chronic ordinary urticaria.
Molecular mechanisms in the formation of the medial longitudinal fascicle
Authors: Ahsan Mansoor , Riley Kerry‐lyn , Schubert Frank R.
Published: July 2007

The first neurons in the vertebrate brain form a stereotypical array of longitudinal and transversal axon tracts, the early axon scaffold. This scaffold is thought to lay down the basic structure for the later, more complex neuronal pathways in the brain. The ventral longitudinal tract is pioneered by neurons located at the ventral midbrain–forebrain boundary, which form the medial longitudinal fascicle. Recent studies have shed some light on the molecular mechanisms that control the development of the medial longitudinal fascicle. Here, we show that patterning molecules, notably the ventralizing signalling molecule Shh, are involved in the formation of medial longitudinal fascicle neurons and in medial longitudinal fascicle axon guidance. Downstream of Shh, several homeobox genes are expressed in the tegmentum. We describe the expression patterns of Sax1, Emx2, Six3, Nkx2.2 and Pax6 in the mesencephalon and pretectum in detail. Furthermore, we review the evidence of their molecular interactions, and their involvement in neuronal fate specification. In particular, Sax1 plays a major role in fate determination of medial longitudinal fascicle neurons. Finally, we discuss the available data on axon guidance mechanisms for the medial longitudinal fascicle, which suggest that different guidance molecules such as class 3 Semaphorins, Slits and Netrins act to determine the caudal and ventral course of the medial longitudinal fascicle axons.
Leucine‐rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson’s disease R1441C/G mutants
Authors: Li Xianting , Tan Yin‐Cai , Poulose Shibu , Olanow C. Warren , Huang Xin‐Yun , Yue Zhenyu
Published: July 2007

Mutations in Leucine‐rich repeat kinase 2 (LRRK2) are linked to the most common familial forms and some sporadic forms of Parkinson’s disease (PD). The LRRK2 protein contains two well‐known functional domains, MAPKKK‐like kinase and Rab‐like GTPase domains. Emerging evidence shows that LRRK2 contains kinase activity which is enhanced in several PD‐associated mutants of LRRK2. However, the GTPase activity of LRRK2 has yet to be formally demonstrated. Here, we produced and purified the epitope‐tagged LRRK2 protein from transgenic mouse brain, and showed that purified brain LRRK2 possesses both kinase and GTPase activity as assayed by GTP binding and hydrolysis. The brain LRRK2 is associated with elevated kinase activity in comparison to that from transgenic lung or transfected cultured cells. In transfected cell cultures, we detected GTP hydrolysis activity in full‐length as well as in GTPase domain of LRRK2. This result indicates that LRRK2 GTPase can be active independent of LRRK2 kinase activity (while LRRK2 kinase activity requires the presence of LRRK2 GTPase as previously shown). We further found that PD mutation R1441C/G in the GTPase domain causes reduced GTP hydrolysis activity, consistent with the altered enzymatic activity in the mutant LRRK2 carrying PD familial mutations. Therefore, our study shows the biochemical characteristics of brain‐specific LRRK2 which is associated with robust kinase and GTPase activity. The distinctive levels of kinase/GTPase activity in brain LRRK2 may help explain LRRK2‐associated neuronal functions or dysfunctions in the pathogenesis of PD.
Translation of striatal‐enriched protein tyrosine phosphatase (STEP) after β1‐adrenergic receptor stimulation
Authors: Hu Yaer , Zhang Yang , Venkitaramani Deepa V. , Lombroso Paul J.
Published: July 2007

The β‐adrenergic system is implicated in long‐term synaptic plasticity in the CNS, a process that requires protein synthesis. To identify proteins that are translated in response to β‐adrenergic receptor stimulation and the pathways that regulate this process, we investigated the effects of isoproterenol on the translation of striatal‐enriched protein tyrosine phosphatase (STEP) in both cortico‐striatal slices and primary neuronal cultures. Isoproterenol stimulation induced a rapid dose‐dependent increase in STEP expression. Anisomycin blocked the increase in STEP expression while actinomycin D had no effect, suggesting a translation‐dependent mechanism. Isoproterenol‐induced STEP translation required activation of β1‐receptors. Application of the MAPK/ERK kinase (MEK) inhibitor SL327 blocked both isoproterenol‐induced activation of pERK and subsequent STEP translation. Inhibitors of PI3K (LY294002) or mTOR (rapamycin) also completely blocked STEP translation. These results suggest that co‐activation of both the ERK and PI3K‐Akt‐mTOR pathways are required for STEP translation. As one of the substrates of STEP includes ERK itself, these results suggest that STEP is translated upon β‐adrenergic activation as part of a negative feedback mechanism.
Identification and characterization of SV31, a novel synaptic vesicle membrane protein and potential transporter
Authors: Burré Jacqueline , Zimmermann Herbert , Volknandt Walter
Published: July 2007

Synaptic vesicle proteins govern all relevant functions of the synaptic vesicle life cycle, including vesicle biogenesis, vesicle transport, uptake and storage of neurotransmitters, and regulated endocytosis and exocytosis. In spite of impressive progress made in the past years, not all known vesicular functions can be assigned to defined protein components, suggesting that the repertoire of synaptic vesicle proteins is still incomplete. We have identified and characterized a novel synaptic vesicle membrane protein of 31 kDa with six putative transmembrane helices that, according to its membrane topology and phylogenetic relation, may function as a vesicular transporter. The vesicular allocation is demonstrated by subcellular fractionation, heterologous expression, immunocytochemical analysis of brain sections and immunoelectron microscopy. The protein is expressed in select brain regions and contained in subpopulations of nerve terminals that immunostain for the vesicular glutamate transporter 1 and the vesicular GABA transporter VGaT (vesicular amino acid transporter) and may attribute specific and as yet undiscovered functions to subsets of glutamatergic and GABAergic synapses.
Mortality, oxidative stress and tau accumulation during ageing in parkin null mice
Authors: Rodríguez‐Navarro Jose A. , Casarejos M. José , Menéndez Jaime , Solano Rosa M. , Rodal Izaskun , Gómez Ana , Yébenes Justo García de , Mena Maria A.
Published: July 2007

Young parkin null (pk−/−) mice have subtle abnormalities of behaviour, dopamine (DA) neurotransmission and free radical production, but no massive loss of DA neurons. We investigated whether these findings are maintained while ageing. Pk−/− mice have reduced life span and age‐related reduced exploratory behaviour, abnormal walking and posture, and behaviours similar to those of early Parkinson’s disease (PD), reduced number of nigrostriatal DA neurons and proapoptotic shifts in the survival/death proteins in midbrain and striatum. Contrary to young pk−/− animals 24‐month‐old pk−/− mice do not have compensatory elevation of GSH in striatum, glutathione reductase (GR) and glutathione peroxidase (GPx) activities are increased and catalase unchanged. Aged pk−/− mice accumulate high levels of tau and fail to up‐regulate CHIP and HSP70. Our results suggest that aged pk−/− mice lack of the compensatory mechanisms that maintain a relatively normal DA function in early adulthood. This study could help to explain the effects of ageing in patients with genetic risks for Parkinson’s disease.
Light exposure causes functional changes in the retina: increased photoreceptor cation channel permeability, photoreceptor apoptosis, and altered retinal metabolic function
Authors: Yu Tzu‐Ying , Acosta Monica L. , Ready Sarah , Cheong Yih‐Liang , Kalloniatis Michael
Published: July 2007

Light exposure induces retinal photoreceptor degeneration and retinal remodeling in both the normal rat retina and in animal models of retinal degeneration. Although cation entry is one of the triggers leading to apoptosis, it is unclear if this event occurs in isolation, or whether a number of pathways lead to photoreceptor apoptosis following light exposure. Following light exposure, we investigated the characteristics of cation entry, apoptotic markers [using terminal deoxynucleotidyl transferase (EC 2.7.7.31) dUTP nick‐end labeling (TUNEL) labeling] and metabolic properties of retina from Sprague–Dawley (SD) rats and a rat model of retinitis pigmentosa [proline‐23‐histidine (P23H) rat]. Assessment of cation channel permeability using agmatine (AGB) labeling showed that excessive cation gating accompanied the series of anomalies that occur prior to photoreceptor loss. Increased AGB labeling in photoreceptors was seen in parallel with the appearance of apoptotic photoreceptors detected by TUNEL labeling with only a smaller proportion of cells colocalizing both markers. However, SD and P23H retinal photoreceptors differed in the amounts and colocalization of AGB gating and TUNEL labeling as a function of light exposure. Finally, reduced retinal lactate dehydrogenase levels were found in SD and P23H rat retinas after a 24‐h light exposure period. Short‐term (2 h) exposure of the P23H rat retina caused an increase in lactate dehydrogenase activity suggesting increased metabolic demand. These results suggest that energy availability may be exacerbated during the early stages of light exposure in susceptible retinas. Also, the concomitant observation of increased ion gating and TUNEL labeling suggest the existence of at least two possible mechanisms in light‐damaged retinas in both SD and the P23H rat retina.
Do life‐ or school‐satisfaction and self‐esteem indicators explain the oral hygiene habits of schoolchildren?
Authors: Honkala S. , Honkala E. , Al‐Sahli N.
Published: July 2007

Abstract –  Objectives:  The aim of this study was to ascertain how frequently toothbrushing and flossing are practiced among schoolchildren in Kuwait and whether life‐ and school‐satisfaction and self‐esteem indicators are associated with oral hygiene habits.

Methods:  A sample of 2312 schoolchildren between 11 and 13 years old filled out a structured questionnaire anonymously in school classrooms during 2002 and 2003. For this study, nationally representative samples of children were drawn from all six governorates of Kuwait. Only government schools were included. The questionnaire of the Health Behaviour in School‐Aged Children Study was used in this study after it was modified to suit Kuwait. A chi‐squared test and logistic regression model were used for analyzing the data.

Results:  Over half of the pupils reported brushing their teeth more than once a day; girls reported brushing more frequently than boys did. One‐fifth of the pupils did not brush their teeth even on a daily basis. The life‐ and school‐satisfaction and self‐esteem indicators were associated with more‐than‐once‐a‐day toothbrushing frequency. The strongest predictors for recommended brushing were: feeling very happy (OR 2.0, 95% CI 1.38–2.77), feeling that other pupils always accept him/her (1.5; 1.16–2.02), never/sometimes feeling lonely and feeling that it is very easy to make friends (1.4; 1.06–1.94). The summary variables of life‐satisfaction, school‐satisfaction and self‐esteem seemed to be strongly associated with brushing. Dental floss was never used by 45% of the children, weekly by 18% and daily by 17%; 20% did not even know what dental floss was.

Conclusions:  Among intermediate schoolchildren in Kuwait, oral hygiene practices were far behind the international recommendations. Special emphasis should be placed on children who have personal problems with their life, school and self‐esteem.
Risk indicators for dental caries using the International Caries Detection and Assessment System (ICDAS)
Authors: Ismail Amid I. , Sohn Woosung , Tellez Marisol , Willem Jenefer M. , Betz James , Lepkowski James
Published: July 2007

Abstract –  Background:  While national surveys have found that African–Americans have a higher prevalence and severity of dental caries than white‐Americans, there are only a few descriptive studies of the prevalence and severity of dental caries in low‐income urban African–Americans.

Objectives:  This study assessed the prevalence, severity and determinants of dental caries, using the International Caries Detection and Assessment System (ICDAS).

Methods:  A representative sample of low‐income families (a caregiver and a child aged 0–5 years) was selected from low‐income census tracts in the city of Detroit, Michigan. Of the 12,655 randomly selected housing units, 10,695 were occupied and 9781 were successfully contacted (91.5%). There were 1386 families with eligible children in the contacted households; and of those, 1021 were interviewed and examined at a permanent examination center organized for this study. This represents an overall response rate of 73.7%. At the center, trained staff interviewed the main caregivers of the selected children, and trained and calibrated dentists examined the caregiver and her/his child. Data used in this study included information gathered from the social, behavioral and parenting questionnaires, the Block Food Frequency Questionnaire (total sugar intake), and data collected from community and census databases.

Results:  Over 90% of the adults (ages 14–70 years, average 29.3) had at least one noncavitated carious lesion and 82.2% had at least one primary cavitated lesion. Negative binomial regression models found that the age of caregivers and the number of churches in neighborhoods were negatively associated with the number of noncavitated tooth surfaces. Cavitated tooth surfaces were positively associated with age, oral hygiene status, being worried about teeth, a recent visit to a dentist, and the number of grocery stores in the neighborhoods. However, the number of cavitated tooth surfaces was negatively associated with preventive dental visits, positive rating of oral health status and the number of dentists in a community.

Conclusions:  Dental caries, especially at the noncavitated stage, is highly prevalent in low‐income African–American adults in Detroit. A significant increase in the mean number of missing teeth was observed after the age of 34 years. This study found that different individual, social, and community risk indicators were associated with noncavitated versus cavitated tooth surfaces.
The molecular makeup and function of regulatory and effector synapses
Authors: Reichardt Peter , Dornbach Bastian , Gunzer Matthias
Published: July 2007

Summary:  Physical interactions between T cells and antigen‐presenting cells (APCs) form the basis of any specific immune response. Upon cognate contacts, a multimolecular assembly of receptors and adhesion molecules on both cells is created, termed the immunological synapse (IS). Very diverse structures of ISs have been described, yet the functional importance for T‐cell differentiation is largely unclear. Here we discuss the principal structure and function of ISs. We then focus on two characteristic T‐cell–APC pairs, namely T cells contacting dendritic cells (DCs) or naive B cells, for which extremely different patterns of the IS have been observed as well as fundamentally different effects on the function of the activated T cells. We provide a model on how differences in signaling and the involvement of adhesion molecules might lead to diverse interaction kinetics and, eventually, diverse T‐cell differentiation. We hypothesize that the preferred activation of the adhesion molecule leukocyte function‐associated antigen‐1 (LFA‐1) and of the negative regulator for T‐cell activation, cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4), through contact with naive B cells, lead to prolonged cell–cell contacts and the generation of T cells with regulatory capacity. In contrast, DCs might have evolved mechanisms to avoid LFA‐1 overactivation and CTLA‐4 triggering, thereby promoting more dynamic contacts that lead to the preferential generation of effector cells.
Convergence of immunoreceptor and integrin signaling
Authors: Abram Clare L. , Lowell Clifford A.
Published: July 2007

Summary:  A common signaling pathway is known to operate downstream of immunoreceptors, such as the T‐cell, B‐cell, or Fc receptors, following engagement by their respective ligands. This pathway involves Src family kinase‐mediated tyrosine phosphorylation of immunoreceptor tyrosine‐based activation motifs (ITAMs) that recruit and activate spleen tyrosine kinase (Syk) or Zap70 (ζ‐associated protein of 70 kDa) kinases, which in turn activate a variety of downstream signals. Evidence has been building from a variety of sources, particularly mouse models, that molecules involved in the immunoreceptor signaling pathway are also required for signals initiated by integrins. Integrins are the major cell surface receptors that mediate adhesion of leukocytes to a variety of extracellular matrix proteins and counter‐receptors expressed on endothelial cells. Integrin ligation is a critical step in the activation of leukocyte effector functions (such as neutrophil degranulation or lymphocyte proliferation). Integrin signaling through pathways common to those utilized by immunoreceptors provides a mechanism by which leukocyte adhesion can regulate activation of cellular responses. In animal models, integrin‐mediated signal transduction plays a critical role in inflammatory disease. In this review, we discuss the convergence of immunoreceptor and integrin signaling, focusing on how these pathways modulate leukocyte activation.
Integrin modulation and signaling in leukocyte adhesion and migration
Authors: Rose David M. , Alon Ronen , Ginsberg Mark H.
Published: July 2007

Summary:  The movement of leukocytes from the blood into peripheral tissues plays a key role in immunity as well as chronic inflammatory and autoimmune diseases. The shear force of blood flow presents special challenges to leukocytes as they establish adhesion on the vascular endothelium and migrate into the underlying tissues. Integrins are a family of cell adhesion and signaling molecules, whose function can be regulated to meet these challenges. The affinity of integrins for their vascular ligands can be stimulated in subseconds by chemoattractant signaling. This aids in inducing leukocyte adhesion under flow conditions. Further, linkage of these integrins to the actin cytoskeleton also helps to establish adhesion to the endothelium under flow conditions. In the case of α4β1 integrins, this linkage of the integrin to the cytoskeleton is mediated in part by the binding of paxillin to the α4 integrin subunit and the subsequent binding of paxillin to the cytoskeleton molecule talin. The movement of leukocytes along the vascular endothelium and in between endothelial cells requires the temporal and spatial regulation of small guanosine triphosphatases, such as Rac1. We describe mechanisms through which α4β1 integrin signaling regulates appropriate Rac activation to drive leukocyte migration.