bluuebunny/crossref_metadata_2025 huggingface dataset:
Average-case optimality of a hybrid secant-bisection method
Authors: Novak Erich , Ritter Klaus , Woźniakowski Henryk
Published: June 2010

We present an average-case complexity analysis for the zerofinding problem for functions from

C
r

(
[
0
,
1
]
)
,
r
≥
2

{C^r}([0,1]),r \geq 2

, which change sign at the endpoints. This class of functions is equipped with a conditional r-folded Wiener measure. We prove that the average-case complexity of computing an

ε
\varepsilon

-approximation is of order

log
⁡
log
⁡
(
1

/

ε
)

\log \log (1/\varepsilon )

, and that a hybrid secant-bisection method with a suitable adaptive stopping rule is almost optimal. This method uses only function evaluations. We stress that the adaptive stopping rule is crucial. If one uses a nonadaptive stopping rule, then the cost has to be of order

log
⁡
(
1

/

ε
)

\log (1/\varepsilon )

. Hence, the adaptive stopping rule is exponentially more powerful than arbitrary nonadaptive stopping rules. Our algorithm is a slightly simplified version of the hyrbrid methods proposed by Dekker in 1969 and Bus and Dekker in 1975. These algorithms are still considered as "the best algorithms for zerofinding" by Kahaner, Moler, and Nash in their book on numerical methods.
Deciphering subcellular processes in live imaging datasets via dynamic probabilistic networks
Authors: Letinic Kresimir , Sebastian Rafael , Barthel Andrew , Toomre Derek
Published: June 2010

Motivation: Designing mathematical tools that can formally describe the dynamics of complex intracellular processes remains a challenge. Live cell imaging reveals changes in the cellular states, but current simple approaches extract only minimal information of a static snapshot.

Results: We implemented a novel approach for analyzing organelle behavior in live cell imaging data based on hidden Markov models (HMMs) and showed that it can determine the number and evolution of distinct cellular states involved in a biological process. We analyzed insulin-mediated exocytosis of single Glut4-vesicles, a process critical for blood glucose homeostasis and impaired in type II diabetes, by using total internal reflection fluorescence microscopy (TIRFM). HMM analyses of movie sequences of living cells reveal that insulin controls spatial and temporal dynamics of exocytosis via the exocyst, a putative tethering protein complex. Our studies have validated the proof-of-principle of HMM for cellular imaging and provided direct evidence for the existence of complex spatial-temporal regulation of exocytosis in non-polarized cells. We independently confirmed insulin-dependent spatial regulation by using static spatial statistics methods.

Conclusion: We propose that HMM-based approach can be exploited in a wide avenue of cellular processes, especially those where the changes of cellular states in space and time may be highly complex and non-obvious, such as in cell polarization, signaling and developmental processes.

Contact:  kresimir.letinic@yale.edu; derek.toomre@yale.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Ekphrasis and the Creative Process in Henri Michaux's
En rêvant à partir de peintures énigmatiques
(1972)
Authors: Keohane Elizabeth Geary
Published: June 2010

Ekphrasis is examined here in terms of the creative process behind Henri Michaux's
En rêvant à partir de peintures énigmatiques
(1972), a collection of prose poems inspired by the paintings of René Magritte. Ekphrasis will be primarily understood as a verbal description of a visual work of art; Michaux's use of this technique will be seen to question its traditional boundaries and limitations. Analysing Michaux's exploration of the processes of literary creation through ekphrasis in this text also highlights Magritte's similarly playful interrogation of representation. A central concern here is the ekphrastic work's constant struggle to
dis
engage from its source of inspiration whilst being in itself a prolonged engagement with this source. Michaux's interpretation and manipulation of images (Magritte's paintings) and the literary form (the prose poem) are also explored in terms of his dual status as artist-writer. Given that grainy photographs are the basis of Michaux's initial encounter with many of the paintings described, what is the status of the painting and its potential to generate ekphrasis in the age of mechanical reproduction? How might the ‘visual poetry’ of Magritte be recreated or interpreted in a poetic work?
Translating Non-Figuration: Heather Dohollau's Poems on ‘Pure Visuality’
Authors: O'Connor Clémence
Published: June 2010

This article explores the dialogue between poems by Heather Dohollau and art forms that seem particularly alien to verbal ordering, namely so-called ‘abstract’ canvases by Joan Mitchell (
No Daisies
) and Geneviève Asse (
Sans titre
, 1988). Dohollau's ekphrastic texts relate to the painting's verbal element — its title — which teases us into identifying objects in the painting even as it forbids us to do so. Representational instability is reflected in the free circulation of metaphors set in motion. Words do not aim to dominate their visual counterpart, thus challenging views of ekphrasis as rivalry that are traced from Lessing to the critical rhetoric of W. J. T. Mitchell and his followers. Rather, I argue that Dohollau's poems seek to translate the painting's very resistance to language through specifically poetic resources. Words also aim to recreate art perception in its sensorial, preverbal fabric by emphasizing the haptic involvement of sight. Thus Dohollau's poems gesture towards a visual–verbal bilingualism, transcending the limits of what a single semiotic system can express. In the process, both the form and the ethos of ekphrasis are reinvented.
Travelling Images, Images of Travel in Nicolas Bouvier's
L'Usage du monde
Authors: Topping Margaret
Published: June 2010

Sketches and photographs are a familiar tool of the traveller-writer, who commonly draws on them when transforming experience into a textual narrative. The verbal thus displaces the visual — the latter retained, if at all, as mere illustration — in ways that echo James Heffernan's definition of ekphrasis as the ‘verbal description of visual representation’. Yet Nicolas Bouvier's 1963 travel narrative
L'Usage du monde
challenges conventional conceptions of ekphrasis. Juxtaposing the stark ink drawings of Thierry Vernet — Bouvier's travelling companion — with Bouvier's textual narrative,
L'Usage du monde
shifts representation away from a hierarchical relationship between verbal and visual; it offers instead an account of other cultures that is grounded in polyphony and exchange. This article applies Bouvier's own image of travel as a mosaic to the dual narrative form (or ‘iconotext’, to use Michael Nerlich's term) in order to consider a range of fluid relationships between Bouvier's text and Vernet's drawings. In examining these relationships of amplification, reduction, and absence, the article argues that the plurality of the narrative prompts a rethinking of conventional, binary paradigms of intercultural contact. Ultimately, the iconotextual nature of
L'Usage du monde
can be interpreted as a metaphor for the processes of cultural translation and transculturation that are central to Bouvier's travelling ethos.
Life history of a simultaneously hermaphroditic fish, Diplectrum formosum
Authors: Bubley W. J. , Pashuk O.
Published: June 2010

Sand perch Diplectrum formosum were collected in the Atlantic Ocean waters off the south‐eastern U.S. for life history analyses between April 2001 and July 2004 and ranged in size from 63 to 236 mm standard length (LS) and 0–8 years of age. Diplectrum formosum are simultaneous hermaphrodites that reach 50% sexual maturity at 12·2 months and 122·8 mm LS for testicular tissue and 13·6 months and 129·3 mm LS for ovarian tissue. The gonad contains ovarian and testicular tissue separated by a thin basement membrane, with no means of internal self‐fertilization. Spawning females were found between March and January with a peak of spawning activity in May and a realized spawning periodicity of 2 days, equivalent to a maximum of 168 spawning events per year. Fish with testicular tissue in spawning condition were obtained throughout the year in every month sampled with a maximum frequency between June and September. There were also trends indicating that testicular tissue was more likely to be in spawning condition in the presence of hydrated oocytes within the accessory structure. This may indicate the use of the accessory structure as a storage site for hydrated oocytes until a mate can be located.
Clinicopathological significance and prognostic value of leukemia‐related protein 16 expression in invasive ductal breast carcinoma
Authors: Zhao Po , Lu Yali , Han Weidong
Published: June 2010

To explore the expression ofleukemia‐related protein 16 (LRP16)in invasive ductal breast carcinoma and analyze its correlation with clinicopathological feature and prognosis, immunohistochemistry was performed on 100 cases of invasive ductal breast carcinoma. Medical records were reviewed and clinicopathological analysis was performed. Leukemia‐related protein 16 expression was detected in 33 of 100 cases (33%) of the invasive ductal breast carcinoma. Expression of LRP16 in carcinoma was obviously higher than that in normal breast tissue. LRP16 protein expression was found in 27.6% (21/76) of carcinoma at stage I and II, and 50.0% (12/24) of carcinoma at stage III and IV. LRP16 expression was found correlative with metastasis in the axillary lymph node (P = 0.001), stage (P = 0.042), estrogen receptor (ER) expression (P = 0.001), fragile histidine triad (FHIT) expression (P = 0.015) and CD133 expression (P = 0.038), but not with grade (P = 0.543), tumor size (P = 0.263), age (P = 0.840), menopause (P = 0.701) andHER‐2gene amplification (P = 0.463). The difference of the mean disease free survival (DFS) time between cancer patients with LRP16 expression (43.7 months) and those without (77.7 months) was statistically significant (Log rank = 9.989,P = 0.002). The difference of the mean overall survival (OS) time between cancer patients with LRP16 expression (50.0 months) and those without (120.0 months) was statistically significant (Log rank = 9.977,P = 0.002). Our finding suggests that expression of LRP16 protein is correlated with the stage, metastasis, prognosis and expression of ER, progesterone receptor, Ki‐67, CD133 and FHIT in invasive ductal breast carcinoma. (Cancer Sci2010)
Identification of a lung cancer antigen evading CTL attack due to loss of human leukocyte antigen (HLA) class I expression
Authors: Baba Tetsuro , Hanagiri Takeshi , Takenoyama Mitsuhiro , Shiota Hironobu , Kuroda Koji , Shigematsu Yoshiki , Ichiki Yoshinobu , Uramoto Hidetaka , So Tomoko , Yasumoto Kosei
Published: June 2010

The human lung cancer cell line, C831L, lost HLA class I expression due to a mutation of the β2‐microglobulin (β2m) gene, and it may have been the result of immunoediting by CTL cytotoxicity. By restoration of HLA class I expression, we could identify the antigen that may be associated with HLA downregulation. Such an antigen might be a promising target of immunotherapy because it potentially may induce a sufficient immune response to eradicate cancer cells. The CTL clone could be established from lymph node lymphocytes in patient C831 by stimulation with wild‐type β2m‐transduced C831L (C831L‐wβ2m). The CTL clone showed reactivity against C831L‐wβ2m in a HLA‐B*0702‐restricted manner, but not Parental‐C831L or autologous normal cells. The cDNA expression cloning method was used to identify the antigen coding gene recognized by the CTL clone. The cDNA clone exhibited a homology with a part of the mRNA that codes for leucine rich repeat containing eight family member A (LRRC8A). A transfection analysis of minigenes indicated that the antigen peptide was derived from protein translated from the downstream of the registered open reading frame in LRRC8A mRNA. The antigenic 9‐mer peptide (GPRESRPPA) was identified. The present methodology should be useful to find the crucial tumor antigens, which are potentially associated with loss of HLA expression. Furthermore, such an antigen may help in achieving a better understanding of the immunological escape mechanisms and it may also provide a favorable immune response in cancer immunotherapy. (Cancer Sci 2010; 00: 000–000)
The effect of desflurane on filtration performance of breathing system filters*
Authors: Poonawala Y. , Wilkes A. R. , Cann C. , Hall J. E.
Published: June 2010

This study assessed the effect of desflurane on the filtration performance of six breathing system filters intended for use with adults. Three filters contained an electrostatic filter material and three contained a pleated glass fibre filter material. Five samples of each model of filter were exposed to 6% v/v of desflurane for 1 h, 12% v/v of desflurane for 1 h, 12% v/v of desflurane for 4 h and air only for 1 h. Five samples of each filter were also tested without exposure to any vapour or air. The filtration performance was measured by challenging each filter with an aerosol of sodium chloride particles using a Moore’s test rig. Penetration of particles through the electrostatic filters increased following exposure to a higher concentration of desflurane for a longer duration (p < 0.001). The effect on two of the pleated filters was not significant (p = 0.55 and p = 0.64). The effect on the remaining pleated filter was significant (p < 0.001) but small. The efficiency of some filters decreases when they are exposed to high concentrations of desflurane for a long duration. This effect appears more marked in electrostatic filters compared with pleated filters.
Stable isotope analysis reveals detrital resource base sources of the tree hole mosquito, Aedes triseriatus
Authors: KAUFMAN MICHAEL G. , PELZ‐STELINSKI KIRSTEN S. , YEE DONALD A. , JULIANO STEVEN A. , OSTROM PEGGY H. , WALKER EDWARD D.
Published: June 2010

1. Detritus that forms the basis for mosquito production in tree hole ecosystems can vary in type and timing of input. We investigated the contributions of plant‐ and animal‐derived detritus to the biomass of Aedes triseriatus (Say) pupae and adults by using stable isotope (15N and 13C) techniques in laboratory experiments and field collections.

2. Laboratory‐reared mosquito isotope values reflected their detrital resource base, providing a clear distinction between mosquitoes reared on plant or animal detritus.

3. Isotope values from field‐collected pupae were intermediate between what would be expected if a single (either plant or animal) detrital source dominated the resource base. However, mosquito isotope values clustered most closely with plant‐derived values, and a mixed feeding model analysis indicated tree floral parts contributed approximately 80% of mosquito biomass. The mixed model also indicated that animal detritus contributed approximately 30% of mosquito tissue nitrogen.

4. Pupae collected later in the season generally had isotope values that were consistent with an increased contribution from animal detritus, suggesting that this resource became more nutritionally important for mosquitoes as plant inputs declined over the summer.
Wolbachia infection in the tribe Naupactini (Coleoptera, Curculionidae): association between thelytokous parthenogenesis and infection status
Authors: Rodriguero M. S. , Confalonieri V. A. , Guedes J. V. C. , Lanteri A. A.
Published: June 2010

Several parthenogenetic species of broad‐nosed weevils exist, some of them of economic importance because of their pest status. Screening of the maternally inherited Wolbachia bacterium in 29 weevils of the tribe Naupactini, using multilocus sequence typing allowed us to assess a significant correlation between asexuality and infection, and suggests an involvement of Wolbachia in the origin of this reproductive mode. The nine Wolbachia strains retrieved from the Naupactini belong to the B supergroup. Phylogenetic analysis of these strains, along with other 23 strains obtained from arthropods and nematodes, supports previous hypotheses that horizontal transfer of Wolbachia amongst species from unrelated taxa has been pervasive.
Nurses’ emotional experience of caring for children with burns
Authors: Hilliard Carol , O’Neill Mary
Published: June 2010

Aims and objectives.  The aim of this phenomenological study was to explore the emotions experienced by children’s nurses when caring for children with burns, in addition to ascertaining how the nurses dealt with these emotions.

Background.  The nature of nursing practice is such that it inevitably generates some form of emotional response in nurses. The literature reveals that the manner nurses deal with their emotional experiences can impact on their nursing care.

Design.  The study used Husserlian phenomenology to explore the emotional experiences of eight purposively selected children’s nurses who have worked on the burns unit of an Irish paediatric hospital.

Methods.  Data were collected using in‐depth, unstructured interviews and analysed using Colaizzi’s seven stage framework.

Results.  The phenomenon of participants’ emotional experiences is captured in four themes: (1) caring for children with burns, (2) supporting parents, (3) sustaining nurses’ emotional well‐being, and (4) learning to be a burns nurse. Nursing children with burns generated a myriad of emotions for participants. Burns dressing‐changes, managing burn‐related pain, supporting parents and the impact of busy workloads on the emotional care of children and their parents emerged as the most emotionally challenging aspects of participants’ role. Participants recognised the need to manage their emotional responses and spoke of the benefits of a supportive nursing team.

Conclusions.  The findings offer insights into both the rewarding and challenging aspects of nursing children with burns. Nurses in this environment must be supported to recognise and manage their emotional responses to their work.

Relevance to clinical practice.  Helping nurses to manage the emotional consequences of their work will help to sustain their emotional well‐being, enhance the care received by children and also enable nurses to support parents in their role as partners in care.
Modularity of the Mtr respiratory pathway of Shewanella oneidensis strain MR‐1
Authors: Coursolle Dan , Gralnick Jeffrey A.
Published: June 2010

Four distinct pathways predicted to facilitate electron flow for respiration of externally located substrates are encoded in the genome of Shewanella oneidensis strain MR‐1. Although the pathways share a suite of similar proteins, the activity of only two of these pathways has been described. Respiration of extracellular substrates requires a mechanism to facilitate electron transfer from the quinone pool in the cytoplasmic membrane to terminal reductase enzymes located on the outer leaflet of the outer membrane. The four pathways share MtrA paralogues, a periplasmic electron carrier cytochrome, and terminal reductases similar to MtrC for reduction of metals, flavins and electrodes or to DmsAB for reduction of dimethyl sulphoxide (DMSO). The promiscuity of respiratory electron transfer reactions catalysed by these pathways has made studying strains lacking single proteins difficult. Here, we present a comprehensive analysis of MtrA and MtrC paralogues in S. oneidensis to define the roles of these proteins in respiration of insoluble iron oxide, soluble iron citrate, flavins and DMSO. We present evidence that some periplasmic electron carrier components and terminal reductases in these pathways can provide partial compensation in the absence of the primary component, a phenomenon described as modularity, and discuss biochemical and evolutionary implications.
Efflux of a range of antimalarial drugs and ‘chloroquine resistance reversers’ from the digestive vacuole in malaria parasites with mutant PfCRT
Authors: Lehane Adele M. , Kirk Kiaran
Published: June 2010

Chloroquine‐resistant malaria parasites (Plasmodium falciparum) show an increased leak of H+ ions from their internal digestive vacuole in the presence of chloroquine. This phenomenon has been attributed to the transport of chloroquine, together with H+, out of the digestive vacuole (and hence away from its site of action) via a mutant form of the parasite's chloroquine resistance transporter (PfCRT). Here, using transfectant parasite lines, we show that a range of other antimalarial drugs, as well as various ‘chloroquine resistance reversers’ induce an increased leak of H+ from the digestive vacuole of parasites expressing mutant PfCRT, consistent with these compounds being substrates for mutant forms, but not the wild‐type form, of PfCRT. For some compounds there were significant differences observed between parasites having the African/Asian Dd2 form of PfCRT and those with the South American 7G8 form of PfCRT, consistent with there being differences in the transport properties of the two mutant proteins. The finding that chloroquine resistance reversers are substrates for mutant PfCRT has implications for the mechanism of action of this class of compound.
Phytophthora hydropathica, a new pathogen identified from irrigation water, Rhododendron catawbiense and Kalmia latifolia
Authors: Hong C. X. , Gallegly M. E. , Richardson P. A. , Kong P. , Moorman G. W. , Lea‐Cox J. D. , Ross D. S.
Published: June 2010

A new species of Phytophthora, previously referred to as taxon Dre II, is named Phytophthora hydropathica. It is heterothallic, but all isolates recovered to date are of the A1 compatibility type. Plerotic oospores are produced. Its sporangia are usually obpyriform and are nonpapillate and noncaducous. Isolates of P. hydropathica had nearly identical single‐strand conformation polymorphism (SSCP)‐based DNA fingerprints that are distinct from those of all existing species. Their closest relatives are P. parsiana and P. irrigata. This new species is able to grow at relatively high temperatures, with an optimum of 30°C and a maximum of 40°C. It was frequently isolated from irrigation water during warm summers. This species caused leaf necrosis and shoot blight of Rhododendron catawbiense and collar rot of Kalmia latifolia at two nurseries where irrigation reservoirs yielded P. hydropathica. Its potential impact on other horticultural crops is discussed.
Phenotypic and genetic characterization of Colletotrichum isolates from Belgian strawberry fields
Authors: Van Hemelrijck W. , Debode J. , Heungens K. , Maes M. , Creemers P.
Published: June 2010

Colletotrichum isolates (457) were collected from strawberry plant tissues with and without typical anthracnose symptoms and from symptomless weeds in 19 Belgian strawberry fields. The isolates were characterized based on genetic, morphological and pathological features. Isolates were classified according to rDNA‐ITS sequencing: 97% of 211 representative isolates were C. acutatum, 2%C. gloeosporioides and 1%C. coccodes. The C. acutatum isolates belonged to the intraspecific groups A2 (33%), A3 (5%), A4 (50%), A5 (3%) and A7 (6%). Differences in spore morphology, growth rate and colony colour of a selection of 146 isolates confirmed the genetic grouping. Multiple Colletotrichum genotypes were detected in the same field. There was no association between the most common genotypes and geographic origin, presence or absence of symptoms, nor plant species or plant part. Representative Belgian Colletotrichum isolates were used in pathogenicity tests, together with European and American reference isolates. The C. acutatum A2 and the Belgian C. gloeosporioides isolates were the most aggressive on fruits, followed by C. acutatum A3, A4, A5, A7 and C. coccodes isolates. When inoculated into crowns, C. acutatum A2, A5 and American C. gloeosporioides isolates were the most aggressive, followed by C. acutatum A3 isolates. The A4 and A7 isolates and all European C. gloeosporioides isolates were non‐pathogenic on crowns. These data indicate that an unusually diverse Colletotrichum population is present in Belgium. The traditional differentiation between C. acutatum and C. gloeosporioides as causal agents of fruit and crown rot, respectively, proved not to be valid in Belgian strawberry fields.
Investigation of upper gastrointestinal tract involvement and H. pylori presence in lichen planus: a case–controlled study with endoscopic and histopathological findings
Authors: İzol Belcin , Karabulut Ayse Anil , Biyikoglu Ibrahim , Gonultas Mehmet , Eksioglu Meral
Published: June 2010

Background  Lichen planus (LP) is a common disease of unknown etiology. Rare mucosal involvements like esophageal LP have been reported increasingly. Infectious agents including H. pylori and other autoantigens have been investigated in etiology and association with certain gastrointestinal pathologies have been well documented.

Objectives  The aim of this study is to investigate the upper gastrointestinal tract involvement in LP and to evaluate the possible etiologic role of H. pylori.

Patients, Materials and Methods  49 LP patients and 35 volunteers (without LP) with gastrointestinal symptoms were included in the study as the control group. LP group was divided into subgroups regarding gastrointestinal symptoms. Upper videoendoscopy was performed in both groups and biopsies were taken from suspicious areas for LP, gastrointestinal diseases, H. pylori and examined histopathologically. SPSS 13 was used for the analysis. Groups/subgroups were compared via xi‐square test, Mann‐Whitney U test, and t‐test.

Results  Gastrointestinal symptoms were recorded in 71% of LP group; none of LP patients presented typical esophageal LP. Gastrointestinal diseases were more frequent in LP group than controls, endoscopically. Chronic gastritis (91.8%) was the leading diagnosis in LP patients. Superficial gastritis was significantly higher (13.3%) in LP patients than controls (p = 0.04). LP was not diagnosed in any of the esophageal mucosa biopsies whereas lymphoid follicles were observed significantly higher in control group (p < 0.01) histopathologically. H. pylori positivity was found higher in LP group (81.6%) though statistically insignificant.

Conclusions  We believe upper endoscopy should be performed to investigate esophageal LP and gastrointestinal pathologies especially when LP patient is symptomatic. Although we didn't detect esophageal LP, our study had the limitation of taking biopsies from pathological sites only. Since histopathological examination of normal appearing esophagus may help in diagnosing occult LP, and prevent eventual complications, it may be further evaluated in larger study groups. A new technique, magnification chromoendoscopy, may be useful in detecting esophageal involvement. We believe the possible role of H. pylori in LP is yet to be determined also.
PRECLINICAL STUDY: BRIEF REPORT: Epigenetic modulation at the CCR2 gene correlates with the maintenance of behavioral sensitization to methamphetamine
Authors: Ikegami Daigo , Narita Minoru , Imai Satoshi , Miyashita Kazuhiko , Tamura Rie , Narita Michiko , Takagi Shigemi , Yokomizo Akiko , Takeshima Hideyuki , Ando Takayuki , Igarashi Katsuhide , Kanno Jun , Kuzumaki Naoko , Ushijima Toshikazu , Suzuki Tsutomu
Published: June 2010

The intermittent administration of methamphetamine produces behavioral sensitization to methamphetamine. In the limbic forebrain, mainly including the nucleus accumbens, of mice that had been intermittently treated with methamphetamine, we found a significant increase in mRNA of a chemokine, CCR2. This increase was accompanied by a significant increase in histone H3 lysine 4 (H3K4) trimethylation at its promoter. Interestingly, the maintenance of sensitization to methamphetamine‐induced hyperlocomotion was significantly decreased in CCR2 knockout mice. These findings suggest that increased CCR2 associated with epigenetic modification after the intermittent administration of methamphetamine may be associated with the maintenance of sensitization to methamphetamine‐induced hyperlocomotion.
GENETIC STUDY: FULL ARTICLE: Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes
Authors: Grucza Richard A. , Johnson Eric O. , Krueger Robert F. , Breslau Naomi , Saccone Nancy L. , Chen Li‐Shiun , Derringer Jaime , Agrawal Arpana , Lynskey Michael , Bierut Laura J.
Published: June 2010

Nicotine dependence is moderately heritable, but identified genetic associations explain only modest portions of this heritability. We analyzed 3369 SNPs from 349 candidate genes and investigated whether incorporation of SNP‐by‐environment interaction into association analyses might bolster gene discovery efforts and prediction of nicotine dependence. Specifically, we incorporated the interaction between allele count and age at onset of regular smoking (AOS) into association analyses of nicotine dependence. Subjects were from the Collaborative Genetic Study of Nicotine Dependence and included 797 cases ascertained for Fagerström nicotine dependence and 811 non‐nicotine‐dependent smokers as controls, all of European descent. Compared with main effect models, SNP × AOS interaction models resulted in higher numbers of nominally significant tests, increased predictive utility at individual SNPs and higher predictive utility in a multi‐locus model. Some SNPs previously documented in main effect analyses exhibited improved fits in the joint analysis, including rs16969968 from CHRNA5 and rs2314379 from MAP3K4. CHRNA5 exhibited larger effects in later‐onset smokers, in contrast with a previous report that suggested the opposite interaction (Weiss et al. 2008). However, a number of SNPs that did not emerge in main effect analyses were among the strongest findings in the interaction analyses. These include SNPs located in GRIN2B (P = 1.5 × 10−5), which encodes a subunit of the N‐methyl‐D‐aspartate receptor channel, a key molecule in mediating age‐dependent synaptic plasticity. Incorporation of logically chosen interaction parameters, such as AOS, into genetic models of substance use disorders may increase the degree of explained phenotypic variation and constitutes a promising avenue for gene discovery.
PRECLINICAL STUDY: FULL ARTICLE: Repeated ethanol administration modifies the temporal structure of sucrose intake patterns in mice: effects associated with behavioral sensitization
Authors: Pastor Raúl , Kamens Helen M. , McKinnon Carrie S. , Ford Matthew M. , Phillips Tamara J.
Published: June 2010

Neuroadaptations supporting behavioral sensitization to abused drugs are suggested to underlie pathological, excessive motivation toward drugs and drug‐associated stimuli. Drug‐induced sensitization has also been linked to increased appetitive responses for non‐drug, natural reinforcers. The present research investigated whether ethanol (EtOH)‐induced neural changes, inferred from psychomotor sensitization, can modify consumption and intake dynamics for the natural reinforcer, sucrose. The effects of EtOH‐induced sensitization in mice on the temporal structure of sucrose intake patterns were measured using a lickometer system. After sensitization, sucrose intake dynamics were measured for 1 hour daily for 7 days and indicated more rapid initial approach and consumption of sucrose in EtOH‐sensitized groups; animals showed a shorter latency to the first intake bout and an increased number of sucrose bottle licks during the initial 15 minutes of the 1‐hour sessions. This effect was associated with increased frequency and size of bouts. For the total 1‐hour session, sucrose intake and bout dynamics were not different between groups, indicating a change in patterns of sucrose intake but not total consumption. When sensitization was prevented by the γ‐aminobutyric acid B receptor agonist, baclofen, the increased rate of approach and consumption of sucrose were also prevented. Thus, EtOH‐induced sensitization, and not the mere exposure to EtOH, was associated with changes in sucrose intake patterns. These data are consistent with current literature suggesting an enhancing effect of drug‐induced sensitization on motivational processes involved in reinforcement.
Risk factors associated with moderate‐to‐severe renal dysfunction among heart transplant patients: results from the CAPRI study
Authors: Delgado Juan F. , Crespo‐Leiro María G. , Gómez‐Sánchez Miguel A. , Paniagua María J. , González‐Vílchez Francisco , Vázquez de Prada José A. , Fernández‐Yáñez Juan , Pascual David , Almenar Luis , Martínez‐Dolz Luis , Díaz Beatriz , Roig Eulalia , Segovia Javier , Arizón Jose M. , Garrido Iris , Blasco Teresa , López Javier , Brossa Vicens , Manito Nicolás , Muñiz Javier
Published: June 2010

Delgado JF, Crespo‐Leiro MG, Gómez‐Sánchez MA, Paniagua MJ, González‐Vílchez F, Vázquez de Prada JA, Fernández‐Yáñez J, Pascual D, Almenar L, Martínez‐Dolz L, Díaz B, Roig E, Segovia J, Arizón JM, Garrido I, Blasco T, López J, Brossa V, Manito N, Muñiz J. Risk factors associated with moderate‐to‐severe renal dysfunction among heart transplant patients: results from the CAPRI study. Clin Transplant 2010 DOI: 10.1111/j.1399‐0012.2010.01249.x © 2010 John Wiley & Sons A/S.

Abstract:  The longer survival of patients with heart transplantation (HT) favors calcineurin inhibitor–related chronic kidney disease (CKD). It behoves to identify risk factors. At 14 Spanish centers, data on 1062 adult patients with HT (age 59.2 ± 12.3 yr, 82.5% men) were collected at routine follow‐up examinations. Glomerular filtration rate, GFR, was estimated using the four‐variable MDRD equation, and moderate‐or‐severe renal dysfunction (MSRD) was defined as K/DOQI stage 3 CKD or worse. Time since transplant ranged from one month to 22 yr (mean 6.7 yr). At assessment, 26.6% of patients were diabetic and 63.9% hypertensive; 53.9% were taking cyclosporine and 33.1% tacrolimus; and 61.4% had MSRD. Among patients on cyclosporine or tacrolimus at assessment, multivariate logistic regression identified male sex (OR 0.44), pre‐ and post‐HT creatinine (2.73 and 3.13 per mg/dL), age at transplant (1.06 per yr), time since transplant (1.05 per yr), and tacrolimus (0.65) as independent positive or negative predictors of MSRD. It is concluded that female sex, pre‐ and one‐month post‐HT serum creatinine, age at transplant, time since transplant, and immunosuppression with cyclosporine rather than tacrolimus may all be risk factors for development of CKD ≥ stage 3 by patients with HT.
The Cocaine‐ and Amphetamine‐regulated Transcript (CART) Immunoreactivity in the Amygdala of the Pig
Authors: Równiak M. , Robak A. , Bogus‐Nowakowska K. , Wasilewska B. , Najdzion J. , Majewski M.
Published: June 2010

With 5 figures and 1 table

The distribution and morphology of neurons containing cocaine‐ and amphetamine‐regulated transcript (CART) was investigated in the pig amygdala. CART‐ immunoreactive (CART‐IR) cell bodies were rarely observed in the pig amygdala and most often they were present in the posterior (small‐celled) parts of the basolateral and basomedial nuclei. In all other subdivisions only a small number of randomly scattered pericarya were present. In every region studied the CART‐IR neurons formed a heterogeneous population consisting mostly of small, rounded or slightly elongated cell bodies, with a few poorly branched, smooth dendrites. In general, the morphological features of these cells clearly resembled non‐pyramidal Golgi type II interneurons. Some randomly scattered CART‐IR cell bodies were significantly larger and they demonstrated features of pyramidal‐like Golgi type I projecting neurons. The highest densities of CART‐IR fibres were evident within the central and medial nuclei. Moderate to high expression was found within the large‐celled part of the basolateral nucleus and moderate to low levels in the lateral, basomedial and cortical nuclei. The routine double‐labelling studies with antisera directed against CART and somatostatin (SOM), or neuropeptide Y (NPY), or cholecystokinin (CCK), or vasoactive intestinal peptide (VIP), or substance P (SP) demonstrated that, in general, these peptides do not co‐exist in the CART‐IR neurons. However, small subpopulations of the CART‐IR fibres contained SOM, CCK, VIP or SP together.
Circulating miR‐221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression
Authors: Pu Xing‐xiang , Huang Guo‐liang , Guo Hong‐qiang , Guo Cheng‐cheng , Li Haoran , Ye Shen , Ling Suxia , Jiang Li , Tian Ying , Lin Tong‐yu
Published: June 2010

Background and Aim:  Circulating miRNAs exist in serum and plasma and they can be used as a potential noninvasive molecular marker for colorectal cancer (CRC) diagnosis. The present study was to test the availability of direct amplification of miRNAs from plasma without RNA extraction, and to evaluate its clinical application value in CRC.

Methods:  Plasma miR‐21, miR‐221 and miR‐222 levels were determined in 103 CRC patients and 37 healthy normal controls by quantitative reverse transcription‐polymerase chain reaction. Immunohistochemical staining for p53, carcinoembryonic antigen (CEA), estrogen receptor (ER) and progesterone receptor (PR) was carried out in the same CRC patient cohort. The correlation between miR‐221 levels and protein levels of p53, CEA, ER and PR, clinicopathological features or overall survival was analyzed.

Results:  A standard curve shows a good linearity between the log of sample input and CT values over three orders of magnitude of plasma miR‐21, miR‐221 and miR‐222. ROC curve analysis reveals that the plasma levels of miR‐221 is a potential biomarker for differentiating CRC patients from controls. Kaplan–Meier curve assessment shows that the elevated plasma miR‐221 level is a significant prognostic factor for poor overall survival in CRC patients. The immunohistochemistry analysis demonstrates a significant correlation between plasma miR‐221 level and p53 expression.

Conclusions:  The direct amplification of plasma miR‐221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC and is correlated with p53 expression.
Spiral enteroscopy: A preliminary experience in Asian population
Authors: Ramchandani Mohan , Reddy D. Nageshwar , Gupta Rajesh , Lakhtakia Sandeep , Tandan Manu , Darisetty Santosh , Rao Guduru Venkat
Published: June 2010

Background and Aim:  In spite of recent developments in the field of enteroscopy the small bowel remains the challenging organ to access. The spiral enteroscopy is a novel technique using a special over‐tube (Endo‐Ease Discovery SB) system for deep intubation of the small bowel. The aim of the present study was to evaluate the efficacy of spiral enteroscopy with an Olympus enteroscope (SIF Q 180) in an Asian subset of patients.

Methods:  Between January and March 2010, 11 patients underwent spiral enteroscopies. The indication for the procedure was obscure gastrointestinal bleeding in five patients, Crohn's disease in two, malabsorbtion syndrome in two, Peutz‐Jeghers syndrome in one and Osler Weber Rendu disease in one patient.

Results:  Eleven patients (five male and six female) mean age 41.6 years (range 21–62 years) underwent spiral enteroscopy. Spiral enteroscopy advancement was successful in all patients. The average depth of insertion was 249 cm (range 120–400 cm) past the ligament of Treitz, and the average time for the procedure was 27.8 min (range 20–32 min). The findings included ulcers (n = 3), polyps (n = 1), arteriovenous malformation (n = 2), ulcer with stricture (n = 1), and lymphangiectasia (n = 1). No major complications were observed.

Conclusion:  In conclusion, our initial experience with spiral enteroscopy shows that it is easy to perform, takes less time than balloon assisted enteroscopy and is relatively safe.
Suspicious childhood injury: Formulation of forensic opinion
Authors: Skellern Catherine , Donald Terence
Published: June 2010

Child protection paediatricians have a role as forensic experts in the context of suspicious childhood injury. The task of forensic evaluation of suspicious injury is to reach a conclusion to support legal proceedings. For each injury, one of four conclusions should be reached:

The injury has been caused by another person and is considered to have been inflicted.

The injury is adequately explained by the circumstances of the injury event provided (by the carer or other witnesses).

The injury is self‐inflicted – has been caused by the child's own behaviour as a result of normal childhood activity (with no other person actively involved).

The mechanism or sequence of events leading to the injury remains indeterminate or unclear.

An additional consideration is determining the extent to which an injury incident was foreseeable and therefore preventable, to form an opinion on whether lack of care (neglect) is involved. Opinions reflect a body of knowledge in forensic and medical literature of known mechanisms of injury including biomechanical aspects of tissue injury in trauma scenarios. Limitations in using research documenting injury type and prevalence at different developmental stages is discussed and in particular, the application of such research to support a conclusion that the injury must have been inflicted. Emerging recognition of research documenting injuries that overlap with those found in populations of children thought to have been physically assaulted creates some doubt on previous opinions regarding exclusivity of certain findings in children definitively indicating ‘abuse’. Forensic paediatricians should remain objective, limit their opinions to what can be confidently stated and exercise caution where reasonable doubt exists and avoid speculation.
Lessons learned on lead poisoning in children: One‐hundred years on from Turner's declaration
Authors: Taylor Mark P , Schniering Carolyn A , Lanphear Bruce P , Jones Alison L
Published: June 2010

There is significant emerging evidence showing life‐long negative health, intellectual and socio‐behavioural impacts as a result of childhood blood lead concentrations well below the widely used intervention level of 10 µg/dL. This issue raises serious health concerns for children in several Australian smelting and mining towns. Routine educational and home cleanliness advice to wet mop floors rather than to use a brush and pan to reduce lead exposure risks have been shown to have limited efficacy. This paper argues, as advocated 100 years ago by Queensland doctor Alfred Jefferis Turner, that childhood lead poisoning can only be mitigated via primary prevention and reduction of contaminants at source. Given that the effects of lead exposure are irreversible, there is a strong argument for the application of the precautionary principle to dealing with childhood lead exposure. There is a clear need to improve regulatory controls and emissions management to reduce environmental lead exposure risks.
Allergic rhinitis in children
Authors: Turner Paul J , Kemp Andrew S
Published: June 2010

Allergic rhinitis affects up to 40% of children but is commonly undiagnosed. Careful assessment of nasal symptoms allows for the most appropriate therapeutic options to be chosen. Allergen avoidance is often difficult in practice. Antihistamines are of limited benefit in allergic rhinitis caused by house dust mite and other perennial allergens, where symptoms, predominantly nasal obstruction, are not histamine mediated. In contrast, symptoms triggered by pollen, such as nasal itch, rhinorrhoea and sneezing, are relieved by antihistamines. Intranasal steroids are the treatment of choice for persistent moderate–severe allergic rhinitis and are more effective than antihistamines for relief of nasal obstruction. Failure to respond to intranasal medications is often caused by poor compliance or inefficient use of nasal sprays. Immunotherapy may be a useful, if expensive, option, particularly where symptoms are because of a specific pollen. The benefits of immunotherapy in house dust mite‐induced rhinitis and asthma remain controversial.
Cerebellar cortical output encodes temporal aspects of rhythmic licking movements and is necessary for normal licking frequency
Authors: Bryant Jerí L. , Boughter John D. , Gong Suzhen , LeDoux Mark S. , Heck Detlef H.
Published: June 2010

Rodents consume water by performing stereotypic, rhythmic licking movements that are believed to be controlled by brainstem pattern‐generating circuits. Previous work has shown that synchronized population activity of inferior olive neurons was phase‐locked to the licking rhythm in rats, suggesting a cerebellar involvement in temporal aspects of licking behavior. However, what role the cerebellum has in licking behavior and whether licking is represented in the high‐frequency simple spike output of Purkinje cells remains unknown. We recorded Purkinje cell simple and complex spike activity in awake mice during licking, and determined the behavioral consequences of loss of cerebellar function. Mouse cerebellar cortex contained a multifaceted representation of licking behavior encoded in the simple spike activities of Purkinje cells distributed across Crus I, Crus II and lobus simplex of the right cerebellar hemisphere. Lick‐related Purkinje cell simple spike activity was modulated rhythmically, phase‐locked to the lick rhythm, or non‐rhythmically. A subpopulation of lick‐related Purkinje cells differentially represented lick interval duration in their simple spike activity. Surgical removal of the cerebellum or temporary pharmacological inactivation of the cerebellar nuclei significantly slowed the licking frequency. Fluid licking was also less efficient in mice with impaired cerebellar function, indicated by a significant decline in the volume per lick fluid intake. The gross licking movement appeared unaffected. Our results suggest a cerebellar role in modulating the frequency of the central pattern‐generating circuits controlling fluid licking and in the fine coordination of licking, while contributing little to the coordination of the gross licking movement.
Differential effects of central injections of D1 and D2 receptor agonists and antagonists on male sexual behavior in Japanese quail
Authors: Kleitz‐Nelson H. K. , Cornil C. A. , Balthazart J. , Ball G. F.
Published: June 2010

A key brain site in the control of male sexual behavior is the medial pre‐optic area (mPOA) where dopamine stimulates both D1 and D2 receptor subtypes. Research completed to date in Japanese quail has only utilized systemic injections and therefore much is unknown about the specific role played by dopamine in the brain and mPOA in particular. The present study investigated the role of D1 and D2 receptors on male sexual behavior by examining how intracerebroventricular injections and microinjections into the mPOA of D1 and D2 agonists and antagonists influenced appetitive and consummatory aspects of sexual behavior in male quail. Experiments 1 and 2 investigated the effects of intracerebroventricular injections at three doses of D1 or D2 agonists and antagonists. The results indicated that D1 receptors facilitated consummatory male sexual behavior, whereas D2 receptors inhibited both appetitive and consummatory behaviors. Experiment 3 examined the effects of the same compounds specifically injected in the mPOA and showed that, in this region, both receptors stimulated male sexual behaviors. Together, these data indicated that the stimulatory action of dopamine in the mPOA may require a combined activation of D1 and D2 receptors. Finally, the regulation of male sexual behavior by centrally infused dopaminergic compounds in a species lacking an intromittent organ suggested that dopamine action on male sexual behavior does not simply reflect the modulation of genital reflexes due to general arousal, but relates to the central control of sexual motivation. Together, these data support the claim that dopamine specifically regulates male sexual behavior.