bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrahippocampal Corticosterone Response in Mice Selectively Bred for Extremes in Stress Reactivity: A Microdialysis Study
Authors: Heinzmann J.‐M. , Thoeringer C.‐K. , Knapman A. , Palme R. , Holsboer F. , Uhr M. , Landgraf R. , Touma C.
Published: August 2010

The hypothalamic‐pituitary‐adrenocortical (HPA) axis is one of the major stress hormone systems, and glucocorticoids (GCs) play a pivotal role in homeostatic processes throughout the body and brain. A dysregulation of the HPA axis, leading to an aberrant secretion of GCs, is associated with affective disorders such as major depression. In the present study, three mouse lines selectively bred for high (HR), intermediate (IR) or low (LR) stress reactivity were used to elucidate the temporal dynamics of intrahippocampal corticosterone (CORT) in response to a standardised stressor. In particular, we addressed the question of whether the distinct differences in HPA axis reactivity between the three mouse lines, as determined by plasma CORT measurements, are present in the central nervous system as well, and if the respective endophenotype is brought about by alterations in blood–brain barrier (BBB) functionality. We applied in vivo microdialysis in the hippocampus, demonstrating that the concentrations of CORT released from the adrenals in response to restraint stress are not only distinctly different in the plasma, but can also be found in the central nervous system, although the differences between the three mouse lines were attenuated, particularly between IR and LR animals. Additionally, a time lag of approximately 60 min was observed in all three lines regarding intrahippocampal peak concentrations of CORT after the onset of the stressor. Furthermore, we showed that the penetration and clearance of CORT in the hippocampal tissue was not affected by differences in BBB functionality because the multidrug resistance 1 P‐glycoprotein (Mdr1 Pgp) was equally expressed in HR, IR and LR mice. Furthermore, we could exclude surgical damage of the BBB because peripherally‐injected dexamethasone, which is a high affinity substrate for the Mdr1 Pgp and therefore restricted from entering the brain, could only be detected in the plasma and was virtually absent in the brain.
Comparative immunogenicity of two vaccination schedules of a combined hepatitis A and B vaccine in healthy volunteers
Authors: De Schryver A. , Verstrepen K. , Vandersmissen L. , Vandermeeren N. , Vernaillen I. , Vranckx R. , Van Damme P. , van Sprundel M.
Published: August 2010

Summary.  In 1996, a combined vaccine against both hepatitis A and B was licensed and commercialized and has been recommended for healthcare personnel in Belgium. This study compares the immunogenicity against hepatitis B virus (HBV) and safety of two vaccination schedules (0–1–12 months and 0–1–6 months) with this vaccine. This is a randomized, stratified and controlled study in healthy adult workers, who are not occupationally exposed to HBV. Seroconversion (≥1 IU/L) and seroprotection (≥10 IU/L) rates were compared using Fisher’s exact test; geometric mean concentrations (GMCs) of anti‐HBs were compared using one‐way ANOVA. All statistical analyses were carried out with SPSS 11 on Apple Macintosh. A total of 399 subjects were enrolled in the study, and 356 were analysed according to the protocol. The rate of ≥10 IU/L at 6 months was 70.6% in the group 0–1–12 and 79.9% in the group 0–1–6; this rate decreased to 55.9% at 12 months in the first group. Seroconversion and seroprotective rates against HBV measured at month 13 in group 0–1–12 (98.9% and 95.6%) and measured at month 7 in group 0–1–6 (99.4% and 97.1%) were not statistically significantly different. GMC of anti‐HBs after the 0–1–12 schedule was more than two fold higher than after 0–1–6 schedule (P < 0.001). Reported side effects were comparable in both groups with a slight tendency to fewer side effects in the 0–1–12 group after the third dose. The results from our study show that the completed schedule 0–1–12 offers at least equal protective immunogenicity against HBV as the completed 0–1–6 schedule. People not receiving their third dose at 6 months can be given this dose up to 12 months after the first dose. The drawback of this flexibility, however, is the longer time period before the protection becomes effective.
Asp3 mediates multiple protein–protein interactions within the accessory Sec system of Streptococcus gordonii
Authors: Seepersaud Ravin , Bensing Barbara A. , Yen Yihfen T. , Sullam Paul M.
Published: August 2010

Bacterial binding to human platelets is an important step in the pathogenesis of infective endocarditis. Streptococcus gordonii can mediate its platelet attachment through a cell wall glycoprotein termed GspB (‘gordonii surface protein B’). GspB export is mediated by a seven‐component accessory Sec system, containing two homologues of the general secretory pathway (SecA2 and SecY2) and five accessory Sec proteins (Asps1–5). Here we show that the Asps are required for optimal export of GspB independent of the glycosylation process. Furthermore, yeast two‐hybrid screening of the accessory Sec system revealed interactions occurring between Asp3 and the other components of the system. Asp3 was shown to bind SecA2, Asp1, Asp2 and itself. Mutagenesis of Asp3 identified N‐ and C‐terminal regions that are essential for GspB transport, and conserved residues within the C‐terminal domain mediated Asp3 binding to other accessory Sec components. The loss of binding by Asp3 also resulted in an impaired ability of S. gordonii to secrete GspB. These studies indicate that Asp3 is a central element mediating multiple interactions among accessory Sec components that are essential for GspB transport to the cell surface.
An essential role for UshA in processing of extracellular flavin electron shuttles by Shewanella oneidensis
Authors: Covington Elizabeth D. , Gelbmann Christopher B. , Kotloski Nicholas J. , Gralnick Jeffrey A.
Published: August 2010

The facultative anaerobe Shewanella oneidensis can reduce a number of insoluble extracellular metals. Direct adsorption of cells to the metal surface is not necessary, and it has been shown that S. oneidensis releases low concentrations flavins, including riboflavin and flavin mononucleotide (FMN), into the surrounding medium to act as extracellular electron shuttles. However, the mechanism of flavin release by Shewanella remains unknown. We have conducted a transposon mutagenesis screen to identify mutants deficient in extracellular flavin accumulation. Mutations in ushA, encoding a predicted 5′‐nucleotidase, resulted in accumulation of flavin adenine dinucleotide (FAD) in culture supernatants, with a corresponding decrease in FMN and riboflavin. Cellular extracts of S. oneidensis convert FAD to FMN, whereas extracts of ushA mutants do not, and fractionation experiments show that UshA activity is periplasmic. We hypothesize that S. oneidensis secretes FAD into the periplasmic space, where it is hydrolysed by UshA to FMN and adenosine monophosphate (AMP). FMN diffuses through outer membrane porins where it accelerates extracellular electron transfer, and AMP is dephosphorylated by UshA and reassimilated by the cell. We predict that transport of FAD into the periplasm also satisfies the cofactor requirement of the unusual periplasmic fumarate reductase found in Shewanella.
Importance of the tmRNA system for cell survival when transcription is blocked by DNA–protein cross‐links
Authors: Kuo H. Kenny , Krasich Rachel , Bhagwat Ashok S. , Kreuzer Kenneth N.
Published: August 2010

Anticancer drug 5‐azacytidine (aza‐C) induces DNA–protein cross‐links (DPCs) between cytosine methyltransferase and DNA as the drug inhibits methylation. We found that mutants defective in the tmRNA translational quality control system are hypersensitive to aza‐C. Hypersensitivity requires expression of active methyltransferase, indicating the importance of DPC formation. Furthermore, the tmRNA pathway is activated upon aza‐C treatment in cells expressing methyltransferase, resulting in increased levels of SsrA tagged proteins. These results argue that the tmRNA pathway clears stalled ribosome‐mRNA complexes generated after transcriptional blockage by aza‐C‐induced DPCs. In support, an ssrA mutant is also hypersensitive to streptolydigin, which blocks RNA polymerase elongation by a different mechanism. The tmRNA pathway is thought to act only on ribosomes containing a 3′ RNA end near the A site, and the known pathway for releasing RNA 3′ ends from a blocked polymerase involves Mfd helicase. However, an mfd knockout mutant is not hypersensitive to either aza‐C‐induced DPC formation or streptolydigin, indicating that Mfd is not involved. Transcription termination factor Rho is also likely not involved, because the Rho‐specific inhibitor bicyclomycin failed to show synergism with either aza‐C or streptolydigin. Based on these findings, we discuss models for how E. coli processes transcription/translation complexes blocked at DPCs.
A new role for coenzyme F420 in aflatoxin reduction by soil mycobacteria
Authors: Graham David E.
Published: August 2010

Hepatotoxic aflatoxins have found a worthy adversary in two new families of bacterial oxidoreductases. These enzymes use the reduced coenzyme F420 to initiate the degradation of furanocoumarin compounds, including the major mycotoxin products of Aspergillus flavus. Along with pyridoxal 5′‐phosphate synthases and aryl nitroreductases, these proteins form a large and versatile superfamily of flavin and deazaflavin‐dependent oxidoreductases. F420‐dependent members of this family appear to share a common mechanism of hydride transfer from the reduced, low‐potential deazaflavin to the electron‐deficient ring systems of their substrates.
Mutations affecting Leptospira interrogans lipopolysaccharide attenuate virulence
Authors: Murray Gerald L. , Srikram Amporn , Henry Rebekah , Hartskeerl Rudy A. , Sermswan Rasana W. , Adler Ben
Published: August 2010

Leptospira interrogans is the causative agent of leptospirosis. Lipopolysaccharide (LPS) is the major outer membrane component of L. interrogans. It is the dominant antigen recognized during infection and the basis for serological classification. The structure of LPS and its role in pathogenesis are unknown. We describe two defined mutants of L. interrogans serovar Manilae with transposon insertions in the LPS locus. Mutant M895 was disrupted in gene la1641 encoding a protein with no known homologues. M1352 was disrupted in a gene unique to serovar Manilae also encoding a protein of unknown function. M895 produced truncated LPS while M1352 showed little or no change in LPS molecular mass. Both mutants showed altered agglutination titres against rabbit antiserum and against a panel of LPS‐specific monoclonal antibodies. The mutants were severely attenuated in virulence via the intraperitoneal route of infection, and were cleared from the host animal by 3 days after infection. M895 was also highly attenuated via the mucosal infection route. Resistance to complement in human serum was unaltered for both mutants. While complementation of mutants was not possible, the attenuation of two independently derived LPS mutants demonstrates for the first time that LPS plays an essential role leptospiral virulence.
Mobilizable genomic islands: going mobile with oriT mimicry
Authors: Waldor Matthew K.
Published: August 2010

Many bacterial chromosomes contain genomic islands, large DNA segments that became incorporated into the chromosome following their horizontal transmission. However, the mechanisms that mediate the lateral transfer of genomic islands are for the most part unknown. In this issue of Molecular Microbiology, Daccord et al. describe a new type of transmissible genomic island that can be mobilized by co‐resident integrating conjugative elements (ICEs). These ‘mobilizable genomic islands’ (MGIs) require many ICE‐encoded factors for their transmission, including transcription activators to induce MGI excision, the relaxase to initiate transfer at the MGI oriT and the conjugation machinery to transport MGI DNA to recipient cells. However, MGIs encode their own integrases, which enable their recombination with the chromosome of a new host, as well as a variety of other genes that do not have functions related to mobility. The MGI oriT, which resembles the ICE oriT, can also serve as a site for initiation of ICE‐mediated conjugative transfer of large regions of chromosomal DNA. Overall, these findings raise the possibility that mobilization of chromosomal DNA from cyptic oriTs within genomic islands or elsewhere on the chromosome could be more common place than has been previously appreciated.
A root is a root is a root? Water uptake rates of Citrus root orders
Authors: REWALD BORIS , EPHRATH JHONATHAN E. , RACHMILEVITCH SHIMON
Published: August 2010

Knowledge about the physiological function of root orders is scant. In this study, a system to monitor the water flux among root orders was developed using miniaturized chambers. Different root orders of 4‐year‐old Citrus volkameriana trees were analysed with respect to root morphology and water flux. The eight root orders showed a broad overlap in diameter, but differences in tissue densities and specific root area (SRA) were clearly distinguishable. Thirty per cent of the root branch biomass but 50% of the surface area (SA) was possessed by the first root order, while the fifth accounted for 5% of the SA (20% biomass). The root order was identified as a determinant of water flux. First‐order roots showed a significantly higher rate of water uptake than the second and third root orders, whereas the fourth and fifth root orders showed water excess. The water excess suggested the occurrence of hydraulic redistribution (HR) as a result of differences in osmotic potentials. We suggest that plants may utilize hydraulic redistribution to prevent coarse root desiccation and/or to increase nutrient acquisition. Our study showed that the novel ‘miniature depletion chamber’ method enabled direct measurement of water fluxes per root order and can be a major tool for future studies on root order traits.
Genetic differentiation between hosts and locations in populations of latent Botrytis cinerea in southern England
Authors: Rajaguru B. A. P. , Shaw M. W.
Published: August 2010

This study tested the hypothesis that aggressive, localized infections and asymptomatic systemic infections were caused by distinct specialized groups of Botrytis cinerea, using microsatellite genotypes at nine loci of 243 isolates of B. cinerea obtained from four hosts (strawberry (Fragaria×ananassa), blackberry (Rubus fruticosus agg.), dandelion, (Taraxacum officinale agg.) and primrose (Primula vulgaris)) in three regions in southern England (in the vicinities of Brighton, Reading and Bath). The populations were extremely variable, with up to 20 alleles per locus and high genic diversity. Each host in each region had a population of B. cinerea with distinctive genetic features, and there were also consistent host and regional distinctions. The B. cinerea population from strawberry was distinguished from that on other hosts, including blackberry, most notably by a common 154‐bp amplicon at locus 5 (present in 35 of 77 samples) that was rare in isolates from other hosts (9/166), and by the rarity (3/77) of a 112‐bp allele at locus 7 that was common (58/166) in isolates from other hosts. There was significant linkage disequilibrium overall within the B. cinerea populations on blackberry and strawberry, but with quite different patterns of association among isolates from the two hosts. No evidence was found for differentiation between populations of B. cinerea from systemically infected hosts and those from locally infected fruits.
Diagenesis and sea‐level change: lessons from Moruroa, French Polynesia
Authors: BRAITHWAITE COLIN J. R. , CAMOIN GILBERT F.
Published: August 2010

An inclined borehole through the margin of Moruroa Atoll, French Polynesia, in which the ages of units are constrained by radiometric dates, provides a unique opportunity to examine the relationship between sea‐level change and diagenetic history. The oldest rocks encountered are dated at 355 840 yr bp and the overlying succession records five cycles of deposition and emergence, culminating in the deposition of the Holocene sequence. Successive intervals of emergence provided the driving force for diagenetic change, promoting the through‐flow of chemically aggressive fresh waters that were at times either pervasive or confined within relatively isolated pathways on a millimetre to metre scale. These locally varying flows and flow rates defined restricted zones characterized by differences in water chemistry and diagenetic signatures. In contrast to some sequences elsewhere, the upper part of the Moruroa Atoll succession is typified by alternations of intervals in which either several generations of cement growth are represented or only one or two cements are present. Three distinct diagenetic signatures can be recognized as follows: (i) fresh water phreatic zones are reflected in neomorphism and the deposition of cements that occluded porosity, thus preventing the deposition of later cements and conferring relative stability; (ii) vadose zones are characterized by more complex diagenetic sequences reflecting multiple phases of dissolution and cement growth, attesting to the relative duration of exposure and the conditions of ground water flow; and (iii) deep in the core, sequences reflect lowstand deposits that suffered sub‐sea diagenesis, generating pores in which multi‐layered marine cements apparently formed at more frequent intervals than those subject to subaerial processes. All cements appear to be of narrowly constrained ages. These results highlight the contentious issue of whether the distributions of former diagenetic environments can be related to specific sea‐level stands and erosion surfaces. It seems that, in the Moruroa core, some cycles of sea‐level change are reflected in distinctive packages of diagenetic features that have not been overprinted by cement growths during later sea‐level stands.
Treatment of severe neutropenic sepsis with granulocyte transfusion in the current era – experience from an adult haematology unit in Singapore
Authors: Ang A. L. , Linn Y. C.
Published: August 2010

Objectives: Granulocyte transfusion's (GT) efficacy among adult severe neutropenic sepsis (SNS) patients remains uncertain. We assessed GT's efficacy and its determinants among SNS patients in an adult haematology unit. The feasibility and safety of granulocyte donation (GD) and determinants of granulocyte yield were also evaluated.

Methods: Retrospective analysis of granulocyte donors and recipients from March 2008 to October 2009.

Results:
Donors: Sixty GDs with a median WBC yield (WBCY) of 65·49 (31·30–131·72) × 109 were collected from 48 donors (9 repeat donors) using hydroxyethyl starch and intermittent flow centrifugation aphaeresis after receiving 8 mg dexamethasone and 300 mcg granulocyte colony‐stimulating factor, with no serious adverse reactions (SAR). Six donations were urgently collected <3 h after pre‐medication, the median WBCY of which was not significantly different from donations collected >12 h after pre‐medication [59·18 (45·68–62·90) × 109 vs 67·45 (31·30–131·72) × 109, P = 0·140]. Only pre‐GD absolute neutrophil count (ANC) correlated with WBCY. Patients: Fifteen patients (12 acute leukaemias, 1 severe AA, 1 myelodysplastic syndrome and 1 lymphoma) received median 3 (2–9) ABO/RhD‐matched GTs over 2–24 (median 7) days at 3–61 (median 28) days from severe neutropenia (SN) onset without SAR. They received intensive chemotherapies (N = 9), allogeneic transplant (N = 3), autologous stem cell rescue (N = 1) or immunosuppressants (N = 2). Fourteen had bacterial (N = 1) infections, fungal (N = 3) infections or both (N = 10) and one had severe viral pneumonitis; 63·6 and 30·8% of bacterial and fungal infections responded, respectively. Median ANC increase (ANCincrease) was 1·26 (0–9·25) × 109 at 5–20 (median 11) h post‐GT. On multivariate analysis, each patient's median ANCincrease only significantly correlated positively with median WBC dose/kg (P = 0·013). Five (33·3%) patients survived to discharge; the rest had infection‐related mortality (IRM). IRM was significantly associated with inotropic requirement (P = 0·004), ventilatory requirement (P = 0·017) and persistent SN (P = 0·007).

Conclusion: GD is safe and feasible with good WBCY obtainable using our protocol. The effect of shortening pre‐medication interval on WBCY which may prevent delay in initiating GT is worth evaluating. GT most likely benefits SNS patients with prospects of neutrophil recovery before haemodynamic deterioration. Large randomised trials investigating the role and timing of GT among such patients are required.
Immunomapping of desmosomal and nondesmosomal adhesion molecules in healthy canine footpad, haired skin and buccal mucosal epithelia: comparison with canine pemphigus foliaceus serum immunoglobulin G staining patterns
Authors: Bizikova Petra , Linder Keith E. , Olivry Thierry
Published: August 2010

Pemphigus foliaceus (PF) is the most common canine autoimmune skin disease. In contrast to human PF (hPF), desmoglein‐1 is a minor autoantigen in the canine disease. The major autoantigen(s) of canine PF (cPF) remain(s) unknown, which limits the ability to perform mechanistic studies of lesion formation and the development of novel diagnostic and therapeutic strategies for this disease. The immunofluorescence patterns of selected desmosomal (desmoglein‐1, desmoglein‐3, desmocollin‐1, desmocollin‐3, desmoplakin‐1/2, plakoglobin and plakophilin‐1) and nondesmosomal adhesion proteins (E‐cadherin, claudin‐1, zona occludens‐1 and occludin) in healthy canine footpad, haired skin and buccal mucosal epithelia were determined using hPF and pemphigus vulgaris sera and specific antibodies. The immunostaining patterns were then compared with that of indirect immunofluorescence staining with 66 cPF sera. Most cPF sera (58 of 66; 88%) exhibited positive staining along keratinocyte margins in the stratum spinosum and stratum granulosum of canine footpad. One serum contained autoantibodies binding solely to stratum granulosum keratinocytes. Concurrent intercellular fluorescence in the stratum basale was limited to seven of 66 cPF sera (11%). Only 12 of 66 cPF sera (18%) also exhibited positive IF staining of the buccal mucosa. This study confirms the immunological heterogeneity of cPF immunoglobulin G autoantibodies. Moreover, the major indirect immunofluorescence staining pattern and the inability of most cPF sera to label the buccal mucosa closely matched that of desmocollin‐1. These observations warrant further investigation of desmocollin‐1 as a potential major cPF autoantigen.
Photosynthesis and growth of newly established shoots of Cirsium arvense and Tussilago farfara are resource independent
Authors: NKURUNZIZA L , ROSENQVIST E , STREIBIG J C
Published: August 2010

Nkurunziza L, Rosenqvist E & Streibig JC (2011). Photosynthesis and growth of newly established shoots of Cirsium arvense and Tussilago farfara are resource independent. Weed Research 51, 33–40.

Cirsium arvense and Tussilago farfara are noxious creeping perennial weeds of temperate crops. Cirsium arvense infests both conventional and organic crops, while T. farfara is more common in organic cropping systems. Mechanical control used in organic farming often leaves intact shoots within crop rows. It is unknown whether shoots and rhizomes are affected by cutting adjacent interconnected shoots. In glasshouse experiments, comparison of net photosynthesis, chlorophyll a fluorescence and quantum efficiency (Fv/Fm) of disturbed and undisturbed clones, did not show any disturbance effect. Maximum net photosynthesis decreased over time in both disturbed and undisturbed clones, depending on environmental conditions. Maximum net photosynthesis was not affected by the size of removed shoots and the Fv/Fm did not change much from the theoretical value of 0.83. These results imply that there were no source/sink relations in established shoots acting as feedback control for photosynthesis. The resource sharing via horizontal roots/rhizomes did not exist at the rosette growth stage in homogeneous environments. Therefore, both species do not benefit from their clonal interconnectedness as perennial weeds to cope with disturbances, as compared with annual weeds. Further studies are required to investigate this in heterogeneous environments.
Landform type and land improvement intensity affect floristic composition in rice paddy fields from central Japan
Authors: YAMADA S , KUSUMOTO Y , TOKUOKA Y , YAMAMOTO S
Published: August 2010

Yamada S, Kusumoto Y, Tokuoka Y & Yamamoto S (2011). Landform type and land improvement intensity affect floristic composition in rice paddy fields from central Japan. Weed Research 51, 51–62.

Paddy field agroecosystems are floristically highly diverse, but the mechanisms affecting this diversity are not clear, especially at broad spatial scales. To conserve paddy weed species, we aimed to clarify the importance of landscape‐scale variables for in‐field floristic diversity. Statistical evidence of the shape of the species response along environmental gradients was obtained by Detrended Correspondence Analysis, DCA. Predicted variables were landform type (narrow valley floor, wide valley floor, old river channel, meander plain with dry soil and meander plain with wet soil), intensity of land improvement (six classes) and species attribute. Both landform type and land improvement intensity were important in explaining variations in in‐field floristic diversity. Non‐paddy weeds and rare threatened species occurred frequently in unimproved plots. Plots in the narrow valley floor and old river channel landform categories had representative species that were categorised as threatened. Unimproved plots also had representative species that were categorised as threatened. The threatened representative species in unimproved plots were confined to old river channels. Unimproved plots in old river channels were the most vulnerable in terms of conservation. Estimation of floristic patterns in paddy fields using landform type and land improvement intensity could be a useful tool for maintaining floristic diversity.
Nicotine increases neural response to unpleasant stimuli and anxiety in non‐smokers
Authors: Kobiella Andrea , Ulshöfer Dorothea E. , Vollmert Christian , Vollstädt‐Klein Sabine , Bühler Mira , Esslinger Christine , Smolka Michael N.
Published: August 2010

Studies in smokers suggest that nicotine might exert anxiolytic, stress‐dampening and mood‐enhancing effects and beneficially influences neural processing of affective information. Regarding non‐smokers, results are inconsistent, and no data exist on the effect of nicotine on neural emotion processing. We applied functional magnetic resonance imaging (fMRI) to assess the influence of nicotine on brain activation during processing of emotional stimuli in 31 non‐smokers with a maximum lifetime cigarette consumption of 20 cigarettes. Participants were subjected to two fMRI scans with event‐related presentations of images taken from the International Affective Picture System, receiving nicotine (2 mg) and placebo gums in a double‐blinded, randomized cross‐over design. Furthermore, subjective affect was assessed. Nicotine increased brain activity in response to unpleasant stimuli in the amygdala, anterior cingulate cortex (ACC) and basal ganglia, whereas processing of pleasant stimuli was not altered. Psychophysiological interaction (PPI) analyses revealed that nicotine increased connectivity between the amygdala and the perigenual ACC (pACC) during processing of unpleasant stimuli and decreased connectivity between those structures during processing of pleasant stimuli. Participants reported higher state anxiety under nicotine than placebo. A single dose of nicotine acted as a stressor in non‐smokers, leading to increased anxiety and neural activation elicited by unpleasant stimuli as well as altered connectivity within the amygdala–pACC circuit. Besides the possibility that reactions to nicotine may differ between non‐smokers and smokers due to tolerance and neuroadaptive processes that occur during prolonged nicotine use, a priori differences in smokers and non‐smokers might potentially explain diverse effects of nicotine on affect and emotional reactivity.
MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption
Authors: Nilsson Kent W. , Comasco Erika , Åslund Cecilia , Nordquist Niklas , Leppert Jerzy , Oreland Lars
Published: August 2010

The aim of the present study was to investigate MAOA gene–environment (G*E) interactions in relation to adolescent alcohol consumption. In the county of Västmanland, Sweden, all 17–18‐year‐old students were asked to complete an anonymous questionnaire and provide a saliva sample during class hours. A total of 2263 students completed the questionnaire (77.4%) and a saliva sample was provided by 2131 participants. Failed MAOA u‐variable number of tandem repeats (VNTR) genotype analyses and internal non‐responses left 851 boys and 735 girls (total n = 1586) to be investigated. Alcohol use disorder identification test was used to measure hazardous alcohol consumption. MAOA u‐VNTR was used to measure biological risk in interaction with poor family relations and experience of sexual abuse. The model was also adjusted for non‐independent socioeconomic variables, separated parents, type of housing and parental unemployment. Results showed that the MAOA u‐VNTR, in interaction with psychosocial risk factors, such as the quality of family relations and sexual abuse, was related to high alcohol consumption among adolescents. Girls, carrying the long MAOA u‐VNTR variant showed a higher risk of being high alcohol consumers, whereas among boys, the short allele was related to higher alcohol consumption. The present study supports the hypothesis that there is a relation between MAOA u‐VNTR and alcohol consumption and that this relation is modulated by environmental factors. Furthermore, the present study also supports the hypothesis that there is a sex difference in the G*E interaction.
High cocaine dosage decreases neurogenesis in the hippocampus and impairs working memory
Authors: Sudai Einav , Croitoru Ofri , Shaldubina Alona , Abraham Lital , Gispan Iris , Flaumenhaft Yakov , Roth‐Deri Ilana , Kinor Noa , Aharoni Shai , Ben‐Tzion Moshe , Yadid Gal
Published: August 2010

Drug addiction is a chronic brain disorder, characterized by the loss of the ability to control drug consumption. The neurobiology of addiction is traditionally thought to involve the mesocorticolimbic system of the brain. However, the hippocampus has received renewed interest for its potential role in addiction. Part of this attention is because of the fact that drugs of abuse are potent negative regulators of neurogenesis in the adult hippocampus and may as a result impair learning and memory. We investigated the effects of different dosages of contingent cocaine on cell proliferation and neurogenesis in the dentate gyrus of the hippocampus and on working memory during abstinence, using the water T‐maze test, in adult rats. We found that cocaine, in addition to the changes it produces in the reward system, if taken in high doses, can attenuate the production and development of new neurons in the hippocampus, and reduce working memory.
Lesions of nucleus accumbens affect morphine‐induced release of ascorbic acid and GABA but not of glutamate in rats
Authors: Sun Ji Y. , Yang Jing Y. , Wang Fang , Wang Jian Y. , Song Wu , Su Guang Y. , Dong Ying X. , Wu Chun F.
Published: August 2010

Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine‐induced effects on the neurotransmission of the brain, especially on the release of AA. In the present study, the effects of morphine on the release of extracellular AA, γ‐aminobutyric acid (GABA) and glutamate (Glu) in the NAc following bilateral NAc lesions induced by kainic acid (KA) were studied by using the microdialysis technique, coupled to high performance liquid chromatography with electrochemical detection (HPLC‐ECD) and fluorescent detection (HPLC‐FD). The results showed that local perfusion of morphine (100 µM, 1 mM) in NAc dose‐dependently increased AA and GABA release, while attenuated Glu release in the NAc. Naloxone (0.4 mM) pretreated by local perfusion to the NAc, significantly blocked the effects of morphine. After NAc lesion by KA (1 µg), morphine‐induced increase in AA and GABA were markedly eliminated, while decrease in Glu was not affected. The loss effect of morphine on AA and GABA release after KA lesion could be recovered by GABA agonist, musimol. These results indicate that morphine‐induced AA release may be mediated at least by µ‐opioid receptor. Moreover, this effect of morphine possibly depend less on the glutamatergic afferents, but more on the GABAergic circuits within this nucleus. Finally, AA release induced by local perfusion of morphine may be GABA‐receptor mediated and synaptically localized in the NAc.
Differential region‐specific regulation of α4β2* nAChRs by self‐administered and non‐contingent nicotine in C57BL/6J mice
Authors: Metaxas Athanasios , Bailey Alexis , Barbano Maria Flavia , Galeote Lola , Maldonado Rafael , Kitchen Ian
Published: August 2010

Neuronal nAChR upregulation is the hallmark of chronic nicotine exposure. Neuroplasticity to abused drugs, however, depends on whether their administration is forced by the experimenter or is under the control of the experimental animal. Neuroadaptation to chronic nicotine self‐administration was examined with a yoked‐control paradigm, using nose‐poking as the operating procedure. Freely moving C57BL/6J mice that responded for 0.03 mg/kg/infusion of intravenous nicotine under a continuous schedule of reinforcement (FR‐1), had control over the rate and amount of drug intake that a yoked littermate passively received (n = 11). The impact of response dependency on neurobiological changes in nicotinic and dopaminergic systems was subsequently assessed using quantitative autoradiography. Cytisine‐sensitive [125I]epibatidine binding, [3H]SCH23390, [3H]raclopride and [3H]mazindol were used to label nAChRs with α4β2* subtype properties, D1 and D2 dopaminergic receptors, and dopamine transporters, respectively. During a period of 12 days, self‐administration was reliably initiated and maintained in animals receiving response‐contingent nicotine. Region specific changes in the density of α4β2* nAChRs were found to be dependent on the contingency of nicotine treatment. Higher levels of α4β2* receptor binding were observed in the dorsal lateral geniculate nucleus and the ventral tegmental area of self‐administering mice, compared to non‐contingent animals. Moreover, response‐independent increases in D2 binding were observed following chronic nicotine administration. No change in D1 and DAT binding was observed among groups. These findings indicate regional specific alterations in the regulation of the nicotinic cholinergic system following contingent and non‐contingent nicotine exposure, and underline the importance of response dependency on the development of nicotine addiction.
Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus
Authors: Carson Dean S. , Hunt Glenn E. , Guastella Adam J. , Barber Lachlan , Cornish Jennifer L. , Arnold Jonathon C. , Boucher Aurelie A. , McGregor Iain S.
Published: August 2010

Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self‐administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co‐administered oxytocin. Male Sprague‐Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co‐administered oxytocin significantly reduced methamphetamine‐induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine‐induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction‐relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin‐synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self‐stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.
Cell‐specific effects of variants of the 68‐base pair tandem repeat onprodynorphingene promoter activity
Authors: Rouault Morgane , Nielsen David A. , Ho Ann , Kreek Mary Jeanne , Yuferov Vadim
Published: August 2010

A polymorphic 68‐bp tandem repeat has been identified within the promoter of the human prodynorphin (PDYN) gene. We found that this 68‐bp repeat in thePDYNpromoter occurs naturally up to five times. We studied the effect of the number of 68‐bp repeats, and of a SNP (rs61761346) found within the repeat onPDYNgene promoter activity. Thirteen promoter forms, different naturally occurring combinations of repeats and the internal SNP, were cloned upstream of theluciferasereporter gene, transfected into human SK‐N‐SH, H69, or HEK293 cells. Cells were then stimulated with TPA or caffeine. We found cell‐specific effects of the number of 68‐bp repeats on the transcriptional activity of thePDYNpromoter. In SK‐N‐SH and H69 cells, three or four repeats led to lower expression of luciferase than did one or two repeats. The opposite effect was found in HEK293 cells. The SNP also had an effect onPDYNgene expression in both SK‐N‐SH and H69 cells; promoter forms with the A allele had significantly higher expression than promoter forms with the G allele. These results further our understanding of the complex transcriptional regulation of thePDYNgene promoter.
Implication of dopaminergic projection from the ventral tegmental area to the anterior cingulate cortex in μ‐opioid‐induced place preference
Authors: Narita Minoru , Matsushima Yuki , Niikura Keiichi , Narita Michiko , Takagi Shigemi , Nakahara Kae , Kurahashi Kana , Abe Minako , Saeki Mai , Asato Megumi , Imai Satoshi , Ikeda Kazutaka , Kuzumaki Naoko , Suzuki Tsutomu
Published: August 2010

Despite the importance of prefrontal cortical dopamine in modulating reward, little is known about the implication of the specific subregion of prefrontal cortex in opioid reward. We investigated the role of neurons projecting from the ventral tegmental area (VTA) to the anterior cingulate cortex (ACG) in opioid reward. Microinjection of the retrograde tracer fluorogold (FG) into the ACG revealed several retrogradely labelled cells in the VTA. The FG‐positive reactions were noted in both tyrosine hydroxylase (TH)‐positive and ‐negative VTA neurons. The released levels of dopamine and its major metabolites in the ACG were increased by either the electrical stimulation of VTA neurons or microinjection of a selective μ‐opioid receptor (MOR) agonist, (D‐Ala2,N‐MePhe4,Gly‐ol5) enkephalin (DAMGO), into the VTA. MOR‐like immunoreactivity was seen in both TH‐positive and ‐negative VTA neurons projecting to the ACG. The conditioned place preference induced by intra‐VTA injection of DAMGO was significantly attenuated by chemical lesion of dopaminergic terminals in the ACG. The depletion of dopamine in the ACG induced early extinction of μ‐opioid‐induced place preference. The levels of phosphorylated DARPP32 (Thr34) and phosphorylated CREB (Ser133) were increased in the ACG of rats that had maintained the morphine‐induced place preference, whereas the increases of these levels induced by morphine were blocked by pre‐treatment of a selective dopamine D1 receptor antagonist SCH23390. These findings suggest that VTA‐ACG transmission may play a crucial role in the acquisition and maintenance of μ‐opioid‐induced place preference. The activation of DARPP32 and CREB through dopamine D1 receptors in the ACG could be implicated in the maintenance of μ‐opioid‐induced place preference.
Differences between smokers and non‐smokers in regional gray matter volumes: a voxel‐based morphometry study
Authors: Liao Yanhui , Tang Jinsong , Liu Tieqiao , Chen Xiaogang , Hao Wei
Published: August 2010

Magnetic resonance imaging (MRI) studies showed a link between chronic smoking and structural brain abnormalities. To date, little is known about the long‐term effects of smoking on gray matter deficiencies. MRI study was carried for 44 smokers and 44 matched non‐smokers to assess gray matter volume differences between the two groups. Decreased gray matter volumes were found in left thalamus, medial frontal cortex and anterior cingulate of smokers in comparison to controls. This voxel‐based morphometry study is showing reduction of regional gray matter volume in smokers, which might better guide future research into the pathogenesis of chronic smoking.
Yet another gene mutation: dysfunction in mitochondrial protein quality control causing hereditary ataxia
Authors: Huang K
Published: August 2010

Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28.

Di Bella et al. (2010)

Nature Genetics 42(4): 313–321
The relationship between intimate partner violence and children’s asthma in 10 US states/territories
Authors: Breiding Matthew J. , Ziembroski Jessica S.
Published: August 2010

To cite this article: Breiding MJ, Ziembroski JS. The relationship between intimate partner violence and children’s asthma in 10 US states/territories.Pediatr Allergy Immunol 2011; 22: e95–e100.

Intimate partner violence (IPV) has been shown to negatively impact the health of both the adults who experience IPV and the children who are exposed to IPV. Although IPV experienced by women has been linked to children’s asthma, this study is the first to examine this question among both women and men, and the first study in the United States to examine this question as part of a population‐based data set. In 2005, ten US states/territories administered an IPV module and a children’s asthma module within the Behavioral Risk Factor Surveillance System (BRFSS). Lifetime IPV was assessed by four questions that asked about threatened, attempted, or completed physical violence, as well as unwanted sex, by a current or former intimate partner. The children’s asthma module asked respondents to report whether a randomly selected child in their household had ever been diagnosed with asthma and whether the same child currently had asthma. Women who experienced lifetime IPV, in contrast to women who never experienced IPV, were significantly more likely to report that their children had ever had asthma and currently have asthma. Among men, significant differences were not found when comparing men who reported lifetime IPV to those that did not report lifetime IPV. The results highlight the importance of primary prevention of IPV, as reducing the occurrence of IPV could improve not only the long‐term health of those who experience IPV but also the health of their children.
Prophylactic treatment for hypertension and seizure in a case of allogeneic hematopoietic stem cell transplantation after posterior reversible encephalopathy syndrome
Authors: Fukuyama Tetsuhiro , Tanaka Miyuki , Nakazawa Yozo , Motoki Noriko , Inaba Yuji , Higuchi Tsukasa , Koike Kenichi
Published: August 2010

Fukuyama T, Tanaka M, Nakazawa Y, Motoki N, Inaba Y, Higuchi T, Koike K. Prophylactic treatment for hypertension and seizure in a case of allogeneic hematopoietic stem cell transplantation after posterior reversible encephalopathy syndrome. Pediatr Transplantation 2011: 15: E169–E173. © 2010 John Wiley & Sons A/S.

Abstract:  A six‐yr‐old boy developed PRES after induction chemotherapy for the relapse of acute lymphoblastic leukemia. Two months after PRES, he underwent BMT from an unrelated HLA‐mismatched donor. There were many risk factors for PRES in the BMT including the long‐term use of FK506 and methylprednisolone, grade III graft‐versus‐host disease, thrombotic microangiopathy, and sepsis. Prophylactic treatment for hypertension with nicardipine in conjunction with close monitoring of the magnesium level and the use of valproic acid might be an effective management approach to prevent post‐transplant PRES.
Exophiala jeanselmei infection in solid organ transplant recipients: report of two cases and review of the literature
Authors: Lief M.H. , Caplivski D. , Bottone E. J. , Lerner S. , Vidal C. , Huprikar S.
Published: August 2010

M.H. Lief, D. Caplivski, E.J. Bottone, S. Lerner, C. Vidal, S. Huprikar. Exophiala jeanselmei infection in solid organ transplant recipients: report of two cases and review of the literature. Transpl Infect Dis 2011: 13: 73–79. All rights reserved

Abstract: Dematiaceous fungi are an opportunistic pathogen seen in solid organ transplant recipients. We report 2 cases of Exophiala infection and review the medical literature to summarize the spectrum of disease this pathogen can cause in this patient population.