bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of histamine in short‐ and long‐term effects of methamphetamine on the developing mouse brain
Authors: Acevedo Summer F. , Pfankuch Timothy , Van Meer Peter , Raber Jacob
Published: September 2008

With the rise in methamphetamine (MA) use among women of childbearing age, the potential consequences of MA exposure to the developing brain for cognition in adulthood is a major concern. Histamine might mediate these MA effects. Following MA administration in neonatal mice, histamine levels in brain were elevated and the hypothalamic‐pituitary‐adrenal axis was activated. Co‐administration of MA with the H3 receptor agonist immepip antagonized these effects. The effects of MA on histamine levels and on hypothalamic‐pituitary‐adrenal axis activation at P20 were more pronounced in female than male mice. These sex differences could have contributed to the increased susceptibility of female mice to the detrimental long‐term cognitive effects of MA and the H3/H4 antagonist thioperamide. Following behavioral testing, mice neonatally treated with MA or thioperamide showed reduced levels of the dendritic marker microtubule‐associated protein 2 in the CA3 region of the hippocampus and the enthorhinal cortex. This was not seen in mice neonatally treated with immepip and MA who did not show cognitive impairments, suggesting that these brain areas might be particularly important for the long‐term effects of MA on cognitive function. These data support a role for histamine in the effects of MA on the developing brain.
Oligodendrogenesis of adult neural progenitors: differential effects of ciliary neurotrophic factor and mesenchymal stem cell derived factors
Authors: Rivera Francisco J. , Kandasamy Mahesh , Couillard‐Despres Sebastien , Caioni Massimiliano , Sanchez Rosario , Huber Christophe , Weidner Norbert , Bogdahn Ulrich , Aigner Ludwig
Published: September 2008

The oligodendrogenic program of progenitor cells in the adult CNS follows a sequential process of progenitor proliferation, fate choice, determination, differentiation, maturation and survival. Previously, we described a soluble activity derived from mesenchymal stem cells that induces oligodendrogenesis in adult neural progenitor cells. Here, we hypothesized that ciliary neurotrophic factor might be a candidate for this activity, since (i) it is expressed by mesenchymal stem cells and (ii) it can promote oligodendrogenesis during development. Along the course of the study, we found differential effects by ciliary neurotrophic factor and by the mesenchymal stem cells‐derived activity on neural progenitors. While the mesenchymal stem cells‐derived activity induced oligodendrogenesis at the expense of astrogenesis and promoted oligodendroglial differentiation/maturation, the effect of ciliary neurotrophic factor was restricted to the latter one. This was reflected at the levels of the cell fate determinants Olig1, Olig2, Id2, and the oligodendroglia‐maturation transcription factor GTX/Nkx6.2. Finally, experiments using blocking antibodies excluded ciliary neurotrophic factor to be the mesenchymal stem cell‐derived oligodendroglial activity. In summary, this work provides evidence for differential effects of ciliary neurotrophic factor and mesenchymal stem cells‐derived activity on oligodendrogenesis of adult neural progenitor cells.
The antipsychotic spiperone attenuates inflammatory response in cultured microglia via the reduction of proinflammatory cytokine expression and nitric oxide production
Authors: Zheng Long Tai , Hwang Jaegyu , Ock Jiyeon , Lee Maan Gee , Lee Won‐Ha , Suk Kyoungho
Published: September 2008

Glial activation and neuroinflammatory processes play an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and HIV dementia. Activated glia cells can secrete various proinflammatory cytokines and neurotoxic mediators, which may influence neuronal cell survival. Recent studies have demonstrated that glia cell‐mediated neuroinflammation is also related to the pathophysiology of schizophrenia. In the present study, anti‐inflammatory and neuroprotective effects of antipsychotics were investigated using cultured brain cells as a model. The results showed that spiperone significantly decreased the production of nitric oxide in lipopolysaccharide‐stimulated BV‐2 microglia cells, primary microglia and primary astrocyte cultures. Spiperone also significantly inhibited nitric oxide production in adenosine 5′‐triphosphate (ATP)‐stimulated primary microglia cultures. Spiperone markedly decreased the production of tumor necrosis factor‐alpha in BV‐2 microglia cells. Spiperone attenuated the expression of inducible nitric oxide synthase and proinflammatory cytokines such as interleukin‐1β and tumor necrosis factor‐alpha at mRNA levels in BV‐2 microglia cells. Spiperone inhibited nuclear translocation and DNA binding of the p65 subunit of nuclear factor kappa B (NF‐κB), inhibitor of kappa B (IκB) degradation, and phosphorylation of p38 mitogen‐activated protein kinase in the lipopolysaccharide‐stimulated BV‐2 microglia cells. Moreover, spiperone was neuroprotective, as the drug reduced microglia‐mediated neuroblastoma cell death in the microglia/neuron co‐culture. These results imply that the antipsychotic spiperone has anti‐inflammatory and neuroprotective effects in the central nervous system by modulating glial activation.
Terahertz Digital Holography
Authors: Zhang Y. , Zhou W. , Wang X. , Cui Y. , Sun W.
Published: September 2008

Abstract:  Terahertz (THz) technology is combined with digital holography for THz imaging. The characteristics of the propagation behaviour of the THz pulse in free space are investigated by using numerical simulations. The algorithm is based on the angular spectrum theory. The spatiotemporal coupling of the THz pulse during propagation results in a significant time‐dependent beam diameter and wave front. The two‐dimensional dynamic evolution of the THz pulse passing through an aperture is obtained. The diffraction is time‐dependent as the pulse travels through the object, which can be clearly observed in simulations. The simulation algorithm and result have been used to reconstruct the original object, with the spatiotemporal amplitude recorded by using a charge‐coupled device (CCD). The implementation of THz digital holography is presented and the corresponding experimental result given.
Contouring of Diffused Objects by Using Lensless Fourier Transform Digital Holography and Dual‐Index Immersion Method
Authors: Sheoran G. , Hossain M. , Mehta D. S. , Shakher C.
Published: September 2008

Abstract:  A simple method for contouring of diffused objects by using lensless Fourier transform digital holography and dual‐index immersion method is presented. It is noticed that to get more accurate results speckle noise should be eliminated/reduced from the reconstructed phase map from digital holograms. Speckle noise is handled by 5 × 5 median filtering. Depth contour interval up to a maximum of 0.12 mm could be achieved without making the interference phase fringes overcrowded.
On the Feasibility of Shearographic Imaging of Acoustic Cross‐Modulation
Authors: Kalogiannakis G. , Sarens B. , Van Hemelrijck D. , Glorieux C.
Published: September 2008

Abstract:  The detectability of defects as well as their detection contrast have significantly increased in recent years because of the use of nonlinear variants of the classical non‐destructive acoustic methods. The non‐uniformity of stiffness and hysteresis around the area of a defect results in strong non‐classical acoustic nonlinearity, which can be used to effectively distinguish the presence of defects. Motivated by the latest advances in nonlinear laser Doppler vibrometry and nonlinear ultrasonics, we investigated the potential of shearography to detect the so‐called cross‐modulation effect. This effect arises when a strong, low‐frequency pump wave dynamically changes the elastic response of a defect, so that the amplitude of a weak, high‐frequency probing wave passing through the defect is modulated. As a result, the frequency spectrum of the response contains mixed frequency components, which are directly attributed to the underlying defect.
Effects of Window Size on Accuracy and Spatial Resolution in Windowed Phase‐Shifting Digital Holographic Interferometry1
Authors: Morimoto Y. , Matui T. , Fujigaki M. , Kawagishi N.
Published: September 2008

Abstract:  Phase‐shifting digital holographic interferometry is a new method to measure displacement distribution on the surface of an object. Usually holography has speckle noise, which leads to a large error in the analysis of displacement and strain distributions. We previously proposed windowed phase‐shifting digital holographic interferometry (windowed PSDHI). The use of this method leads to accurate displacement analysis, decreasing the effect of speckle patterns. However, noise reduction involves a defect, which renders the spatial resolution low. In this paper, by comparing the conventional noise reduction method using spatial averaging with the windowed PSDHI on spatial resolution, the effectiveness of noise reduction is discussed.
Identification of Specimen Position and Orientation Using Standard Deviation of Intensity in Phase‐Shifting Digital Holography1
Authors: Fujigaki M. , Ashimura Y. , Matui T. , Morimoto Y.
Published: September 2008

Abstract:  Phase‐shifting digital holography is a useful method to measure the displacement distribution and the strain distribution of an object surface. The complex amplitude distribution of an object surface is obtained as the complex amplitude distribution at a reconstruction distance. It is, however, difficult to measure the reconstruction distance by actual measurement. We discovered that the standard deviation of the intensity on the reconstructed image becomes the maximum value when the reconstruction distance is the same as the actual optical path length. The displacement distributions are obtained for the x‐, y‐ and z‐directions. When the normal direction of an object surface inclines from the z‐direction, the displacements defined on the xyz‐coordinate system should be transformed into the object coordinate system. It is, therefore, required to develop a measurement method of the orientation of the object to obtain the parameters for transforming from the xyz‐coordinate system into the object coordinate system. In this paper, the method to identify the position and the orientation of a specimen using the standard deviation of the intensity distribution is proposed.
Full‐Field Vibration Measurement by Time‐Average Speckle Interferometry and by Doppler Vibrometry – A Comparison
Authors: Moreau A. , Borza D. , Nistea I.
Published: September 2008

Abstract:  Identification of dynamic material properties, non‐destructive testing and study of vibroacoustic behaviour of different structures require the use of complex, pointwise and full‐field measurements, which are capable of providing data for experimental modal analysis or model updating. Nowadays, among other techniques, optical non‐contact techniques represent the favourite choice as they do not add mass, stiffness or damping to the structure under test. When the range of vibration amplitudes allows it, most of these techniques are based on interferometric principles. Development of laser sources and detectors leads to a continuous improvement of vibration measurement techniques. However, a hard choice still has to be made between spatial resolution and temporal resolution. Another difficult choice is between space bandwidth product and energetic sensitivity of the detector. While the number of pixels of a camera is continuously increasing, the pixel size seems limited at its lower end. The paper presents a comparative study of the vibration amplitude fields as measured by two full‐field non‐contact techniques, speckle interferometry and laser Doppler vibrometry, and predicted by finite‐element model. The measurements concern the free and the forced vibrations of a thick, composite plate with free boundaries.
THE IMPACT OF SOLUBLE SALTS ON THE DETERIORATION OF PHARAONIC AND COPTIC WALL PAINTINGS AT AL QURNA, EGYPT: MINERALOGY AND CHEMISTRY*
Authors: MOUSSA A. M. A. , KANTIRANIS N. , VOUDOURIS K. S. , STRATIS J. A. , ALI M. F. , CHRISTARAS V.
Published: September 2008

The wall paintings of Al Qurna in Egypt were studied by means of XRD and ICP–AES in order to determine their mineralogical and chemical composition, and to evaluate the impact of soluble salts on their deterioration, including the identification of the building materials and pigments used. Soluble salts analysis showed that NaCl is the most common soluble salt in the bedrock, ground water and surface water samples. The building materials are affected by the ground water, while the wall paintings in the area are affected by the Upper Egypt climatic conditions, which were studied in order to detect their role in the deterioration cycle in the area.
Adult diet affects lifespan and reproduction of the fruit‐feeding butterflyCharaxes fulvescens
Authors: Molleman Freerk , Ding Jimin , Wang Jane‐Ling , Zwaan Bas J. , Carey James R. , Brakefield Paul M.
Published: September 2008

Fruit‐feeding butterflies are among the longest lived Lepidoptera. While the use of pollen‐derived amino acids byHeliconiusbutterflies has been interpreted as important for the evolution of extended lifespans, very little is known about the life‐history consequences of frugivory. This issue is addressed by investigating effects of four adult diets (sugar, sugar with amino acids, banana, and moistened banana) on lifespan and reproduction in the fruit‐feeding butterflyCharaxes fulvescensAurivillius (Lepidoptera: Nymphalidae). Female butterflies were collected from Kibale National Park, Uganda, and kept individually in cages near their natural habitat and data were collected on lifespan, oviposition, and hatching of eggs. Lifespan in captivity was longer for the sugar and the amino acid cohort, than for the banana cohorts. The longitudinal pattern of oviposition was erratic, with many days without oviposition and few periods with high numbers of eggs laid. Butterflies typically did not lay eggs during their 1st week in captivity and the length of the period between capture and first reproduction was significantly shorter for butterflies fed moistened banana. The length of the reproduction period (first reproduction–last reproduction in captivity) and the reproduction rate (total number of eggs/length of the reproduction period) did not differ significantly between the diet treatments. Those fed with amino acid and moistened banana had significantly higher egg hatchability than those fed with sugar and banana. We found no evidence for a lifespan cost of reproduction. Our results show that (1) femaleC. fulvescenscan use amino acids in their diet for laying fertile eggs, (2) more wing‐wear does correlate with lower survival in captivity (indicating aging in the wild), but not with intensity of reproduction (providing no evidence for reproductive aging), and (3) fruit‐feeding butterflies may be dietary restricted in the field.
Mortality of Rhagoletis indifferens exposed to hydrolyzed protein baits and spinosad in the absence and presence of yeast extract
Authors: Yee Wee L.
Published: September 2008

Western cherry fruit fly, Rhagoletis indifferens Curran (Diptera: Tephritidae), is the major quarantine pest of sweet cherry, Prunus avium (L.) L. (Rosaceae), in the Pacific northwest of the USA and in British Columbia in Canada. Although spinosad bait (GF‐120 NF Naturalyte® Fruit Fly Bait) is used for the control of R. indifferens in this region, the effects of alternate food sources on fly responses to this bait have not been studied. In this study, experiments were conducted to determine mortalities of flies exposed to hydrolyzed protein baits in the presence of sugar only and sugar + yeast extract food. All baits contained Entrust® (termed ‘spinosad alone’). When flies were exposed to GF‐120 with or without added ammonia compounds (uric acid, ammonium acetate, and ammonium carbonate) for 48 h, mortalities were higher in the presence of sugar only than in the presence of sugar + yeast extract, but when flies were exposed to spinosad alone, mortalities were similar in presence of either of the two foods. In another experiment comparing GF‐120, Nu‐Lure, Mazoferm, Baker's yeast extract, and spinosad alone, mortalities in the GF‐120, Mazoferm, and Baker's yeast extract treatments were higher in the presence of sugar only than in the presence of sugar + yeast extract, but in the Nu‐Lure and spinosad alone treatments, mortalities were similar in the presence of either of the two foods. Overall results suggest that the indirect effects of yeast extract food on mortality are dependent on bait type and that mortalities caused by spinosad alone and baits are similar. Nu‐Lure and spinosad alone may have an advantage over other treatments for fly control, because their effects do not appear to be affected by the presence of nitrogenous food.
Relation of constant, daily fluctuating, and ambient feeding temperature to daily and accumulated consumption of yeast autolysate and sucrose by female Queensland fruit fly
Authors: Meats A. , Kelly G.L.
Published: September 2008

Intake rates by the Queensland fruit fly, Bactrocera tryoni (Froggatt) (Diptera: Tephritidae), of yeast autolysate and sucrose were clearly related to temperature in constant thermal regimes, but consumption occurred only in light. In regimes of fluctuating temperature, rates of consumption were not necessarily related to the temperatures that prevailed during the photophase, but were more consistently related to daily mean temperature and best related to day degrees per day above the gonadotrophic threshold of 13.5 °C. Day degrees per day could be related to age‐specific changes in the daily rate of yeast autolysate and sucrose consumption, the rate of accumulated consumption of these foods, and thus the time taken to consume the amount of yeast autolysate known to be required for the attainment of sexual maturity. Consumption rate changed within 1 or 2 days of a change between a gonadotrophic regime and a non‐gonadotrophic one (or vice versa), which is consistent with the known rapid effects of temperature change on ovarian maturation.
Monitoring virulence in Asian rice gall midge populations in India
Authors: Bentur J. S. , Cheralu C. , Rao P. Ram Mohan
Published: September 2008

The Asian rice gall midge, Orseolia oryzae (Wood‐Mason) (Diptera: Cecidomyiidae), is a major pest of rice [Oryza sativa L. (Poaceae)] in India. Breeding resistant varieties and their cultivation has been the main approach to manage this pest. However, the breakdown of resistance conferred by the major genes, deployed one at a time, through evolution of virulent biotypes has become a major setback to this approach. Development of polymerase chain reaction‐based molecular markers for eight of the 10 resistance genes and their possible use in marker‐assisted selection has enabled breeders to pyramid resistance genes for achieving durable resistance. However, the choice of resistance genes needs to be made with a better understanding of the virulence composition of the pest populations in the target area and the genetics of plant resistance and insect virulence, as the rice–gall midge interaction is a gene‐for‐gene one. We adopted a single‐female test and coupled it with a modified F2 screen test to note the virulence composition of gall midge populations and estimated the frequency of virulence alleles for adaptation at three pest endemic locations in India, namely, Warangal, Ragolu, and Raipur. Results on biotype composition showed heterogeneous pest populations in all the tests and at all the locations. Tests at Warangal repeated after 8 years showed a rapid increase in frequency of the virulence allele conferring adaptation to the plant resistance gene Gm2 as compared to that of the allele for adaptation to the resistance gene Gm1. This is probably the first direct measurement of a durability parameter of plant genes conferring insect resistance. Results supported earlier observations that sex‐linked virulence against Gm2 makes it less durable. The sex ratio did not deviate from the expected 1:1 ratio at Warangal, but at Ragolu females outnumbered males.
Is the oral health impact profile measuring up? Investigating the scale’s construct validity using structural equation modelling
Authors: Baker S. R. , Gibson B. , Locker D.
Published: September 2008

Abstract –  Objectives:  The aim of the study was to provide an empirical test of the construct validity of the Oral Health Impact Profile as a measure of Locker’s conceptual model of oral health.

Methods:  A secondary analysis of data from the Ontario Study of Older Adults was carried out using structural equation modelling to assess the degree to which scale items measured the construct they were supposed to measure (within‐construct validity) and whether relations between constructs were as hypothesized by Locker’s model (between‐construct validity).

Results:  The findings indicated that the Oral Health Impact Profile as currently conceived does not have adequate within‐construct validity. Scale items did not always measure the construct they were supposed to measure, some items within a construct were redundant, many measured more than one construct, and the scale did not represent seven separate constructs of oral health as originally devised. Following reconceptualization of the scale, the revised six‐factor 22 item version was a better fit to the data. However, the scale did not have adequate between‐construct validity.

Conclusion:  The present findings do not provide support for the conceptual basis of the Oral Health Impact Profile as a measure of Locker’s model of oral health. The need for further conceptual development of the scale, and Locker’s model, are discussed.
Evaluation of sunscreen products using a reconstructed skin model exposed to simulated daily ultraviolet radiation: relevance of filtration profile and SPF value for daily photoprotection
Authors: Lejeune François , Christiaens François , Bernerd Françoise
Published: September 2008

Background: The recent definition of a standard daily ultraviolet radiation (DUVR) has allowed us to reproduce non‐zenithal sun exposure conditions. Exposure to simulated DUVR induces biological damage in human skin, suggesting the need for an appropriate photoprotection.

Methods: Sunscreen products were evaluated using human reconstructed skin in vitro. Two commercial sunscreens (A and B) having similar sun (burn) protection factor (SPF) values (∼15) but different profiles of transmission over the UVA range were tested on skin models exposed to increasing doses of DUVR. Another pair of sunscreens was also tested. One (product C) had an SPF ∼18 with a well‐balanced UVB–UVA profile and the other (product D) an SPF of ∼27 with low UVA absorption. Biological parameters were assessed by (i) histology, (ii) vimentin immunostaining for dermal fibroblasts, and (iii) analysis of matrix metalloprotease (MMP)‐1 secretion.

Results: Products A and C gave better protection from DUVR with regard to fibroblast alterations and MMP‐1 release compared with products B and D, respectively.

Conclusion: To ensure an efficient daily photoprotection from DUVR, the filtration profile of the product should be well balanced with a sufficient level of UVA absorption. With regard to end points evaluated in this study, our data suggest that a higher SPF value does not compensate for low UVA filtration.
Different narrowband UVB dosage regimens in dark skinned psoriatics: a preliminary study
Authors: Youssef Randa M. , Mahgoub Doaa , Mashaly Heba M. , El‐Nabarawy Eman , Samir Nesreen , El‐Mofty Medhat
Published: September 2008

Background: Psoriasis is a common and relapsing disease, which is both physically and psychologically disabling. Narrowband UVB (NB‐UVB) is used in fair‐skinned population in suberythemogenic doses with good results; however, in the darker skin population (skin types III, IV, V) erythemogenic doses have not been thoroughly investigated.

Aim: A left–right bilateral comparative trial was carried out to compare the suberythemogenic dose of NB‐UVB vs. erythemogenic dose in the treatment of dark‐skinned psoriatic patients.

Patients and methods: The study was conducted on 20 patients with chronic plaque psoriasis. The left side was treated with the dose causing minimal erythema [100% of minimal erythema dose (MED)] while the right side received 70% of this MED (suberythemogenic side).

Results: Our results revealed no statistically significant difference in PASI final and in the percentage of reduction of PASI score between both sides as well as the total number of sessions (P‐value>0.05), while the total cumulative UVB dose on the suberythemogenic side was significantly lower (P‐value<0.001).

Conclusion: Our study recommends reducing the dose regimen of NB‐UVB and consequently the cumulative UVB dose by using the suberythemogenic dosing schedule even in dark skin population.
Transcription factors Sp1 and C/EBP regulate NRAMP1 gene expression
Authors: Richer Etienne , Campion Carole G. , Dabbas Basel , White John H. , Cellier Mathieu F. M.
Published: September 2008

The natural resistance‐associated macrophage protein 1 (Nramp1), which belongs to a conserved family of membrane metal transporters, contributes to phagocyte‐autonomous antimicrobial defense mechanisms. Genetic polymorphisms in the human NRAMP1 gene predispose to susceptibility to infectious or inflammatory diseases. To characterize the transcriptional mechanisms controlling NRAMP1 expression, we previously showed that a 263 bp region upstream of the ATG drives basal promoter activity, and that a 325 bp region further upstream confers myeloid specificity and activation during differentiation of HL‐60 cells induced by vitamin D. Herein, the major transcription start site was mapped in the basal region by S1 protection assay, and two cis‐acting elements essential for myeloid transactivation were characterized by in vitro DNase footprinting, electrophoretic mobility shift experiments, in vivo transfection assays using linker‐mutated constructs, and chromatin immunoprecipitation assays in differentiated monocytic cells. One distal cis element binds Sp1 and is required for NRAMP1 myeloid regulation. Another site in the proximal region binds CCAAT enhancer binding proteins α or β and is crucial for transcription. This study implicates Sp1 and C/EBP factors in regulating the expression of the NRAMP1 gene in myeloid cells.
NDRG2 gene expression in B16F10 melanoma cells restrains melanogenesis via inhibition of Mitf expression
Authors: Kim Aeyung , Yang Young , Lee Myeong‐Sok , Yoo Young Do , Lee Hee Gu , Lim Jong‐Seok
Published: September 2008

NDRG2 (N‐myc downstream‐regulated gene 2) is a candidate tumor suppressor implicated in control of glioblastoma proliferation and dendritic cell differentiation. The microphthalmia‐associated transcription factor (Mitf) plays a crucial role in the melanocyte lineage and in melanoma by controlling survival, differentiation, cell cycle entry and exit, and melanoma metastasis. Identifying upstream regulators of Mitf expression, therefore, remains a key issue. In this study, we aimed to assess whether the candidate tumor suppressor NDRG2 can modulate Mitf expression. Here, we show that NDRG2 acts to prevent cAMP and β‐catenin‐mediated activation of the Mitf promoter, thereby blocking melanogenesis via the downstream Mitf target genes Tyrosinase, Tyrp1 and Dct. The data suggest that NDRG2 impairs melanogenesis by interfering with both the TCF/β‐catenin and cAMP/CREB pathways that are known to stimulate Mitf expression in melanocytes and have major implications for the role of NDRG2 in pigmentation and melanoma progression. Taken together, the results not only identify NDRG2 as a novel regulator of pigmentation, but also potentially a key factor in regulating melanoma progression via Mitf.
Melanophores in the stripes of adult zebrafish do not have the nature to gather, but disperse when they have the space to move
Authors: Takahashi Go , Kondo Shigeru
Published: September 2008

Animal skin pattern is one of the good model systems used to study the mechanism of pattern formation. Molecular genetic studies with zebrafish have shown that pigment cells play a major role in the mechanism of stripe formation. Among the variety of cellular events that may be involved in the mechanism, aggregation of melanophores has been suggested as an important factor for pattern formation. However, only a few experimental studies detected the migration ability of melanophores in vivo. Here, we tried to determine whether melanophores really have the ability to aggregate in the skin of zebrafish. Melanophores in the adult stripes are packed densely and they rarely move. However, when the neighboring pigment cells are killed, they move and regenerate the stripe pattern, suggesting that melanophores retain the migration ability. To analyze the migration, we ablated a part of the melanophores by laser to give free space to the remaining cells; we then traced the migration. Contrary to our expectation, we found that melanophores repulsed one another and dispersed from the aggregated condition in the absence of xanthophores. Apparent aggregation may be forced by the stronger repulsive effect against the xanthophores, which excludes melanophores from the yellow stripe region.
Novel MITF targets identified using a two‐step DNA microarray strategy
Authors: Hoek Keith S. , Schlegel Natalie C. , Eichhoff Ossia M. , Widmer Daniel S. , Praetorius Christian , Einarsson Steingrimur O. , Valgeirsdottir Sigridur , Bergsteinsdottir Kristin , Schepsky Alexander , Dummer Reinhard , Steingrimsson Eirikur
Published: September 2008

Malignant melanoma is a chemotherapy‐resistant cancer with high mortality. Recent advances in our understanding of the disease at the molecular level have indicated that it shares many characteristics with developmental precursors to melanocytes, the mature pigment‐producing cells of the skin and hair follicles. The development of melanocytes absolutely depends on the action of the microphthalmia‐associated transcription factor (MITF). MITF has been shown to regulate a broad variety of genes, whose functions range from pigment production to cell‐cycle regulation, migration and survival. However, the existing list of targets is not sufficient to explain the role of MITF in melanocyte development and melanoma progression. DNA microarray analysis of gene expression offers a straightforward approach to identify new target genes, but standard analytical procedures are susceptible to the generation of false positives and require additional experimental steps for validation. Here, we introduce a new strategy where two DNA microarray‐based approaches for identifying transcription factor targets are combined in a cross‐validation protocol designed to help control false‐positive generation. We use this two‐step approach to successfully re‐identify thirteen previously recorded targets of MITF‐mediated upregulation, as well as 71 novel targets. Many of these new targets have known relevance to pigmentation and melanoma biology, and further emphasize the critical role of MITF in these processes.
Retention of the cyanobacterial neurotoxinβ‐N‐methylamino‐l‐alanine in melanin and neuromelanin‐containing cells – a possible link between Parkinson‐dementia complex and pigmentary retinopathy
Authors: Karlsson Oskar , Berg Cecilia , Brittebo Eva B. , Lindquist Nils Gunnar
Published: September 2008

β‐N‐methylamino‐l‐alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson‐dementia complex (PDC). In PDC, neuromelanin‐containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of3H‐BMAA in mice and frogs, with emphasis on pigment‐containing tissues. Using autoradiography, a distinct retention of3H‐BMAA was observed in melanin‐containing tissues such as the eye and neuromelanin‐containing neurons in frog brain. Analysis of the binding of3H‐BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro‐studies with synthetic melanin revealed a stronger interaction of3H‐BMAA with melanin during synthesis than the binding to preformed melanin. Long‐term exposure to BMAA may lead to bioaccumulation in melanin‐ and neuromelanin‐containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.
Anterior chamber parameters measured by the Pentacam CES after uneventful phacoemulsification in normotensive eyes
Authors: Uçakhan Özlenen Ö. , Özkan Muhip , Kanpolat Ayfer
Published: September 2008

Purpose:  We set out to quantify changes in the anterior chamber volume (ACV), anterior chamber depth (ACD) and anterior chamber angle (ACA) measurements obtained by the Pentacam rotating Scheimpflug camera following uneventful phacoemulsification surgery in normotensive eyes with open iridocorneal angles.

Methods:  We enrolled 44 eyes of 44 consecutive patients undergoing cataract extraction in this prospective study. Patients with a history of glaucoma, angle‐closure glaucoma or any other concurrent ocular disease were excluded. A detailed eye examination including intraocular pressure (IOP) measurement was performed and ACV, ACD and inferior, superior, temporal and nasal ACA measurements were obtained in each patient eye using the Pentacam Comprehensive Eye Scanner (Pentacam CES) before and 3 months after phacoemulsification and intraocular lens (IOL) implantation with temporal clear corneal incision. Data were compared using paired t‐test and one‐way anova.

Results:  Mean preoperative ACV, ACD, ACA and IOP measurements were 164.7 ± 49.8 mm3, 3.0 ± 0.8 mm, 35.7 ± 10.2 ° and 15.8 ± 3.7 mmHg, respectively. Three months postoperatively, mean ACV, ACD, ACA and IOP measurements were 200.9 ± 33.3 mm3, 3.9 ± 0.9 mm, 41.5 ± 6.5 ° and 13.2 ± 3.9 mmHg, respectively. Postoperative mean ACV, ACD and ACA values in all four quadrants were significantly increased (p < 0.0001, p < 0.0001, p < 0.0001, respectively), whereas IOP was significantly reduced (p < 0.0001).

Conclusions:  The Pentacam CES allowed very easy, fast, automatic and non‐contact quantification of the anterior chamber parameters pre‐ and postoperatively in all patient eyes. Measurements obtained confirm that in normotensive eyes with open iridocorneal angles, the ACV and ACD increase and the ACA widens in all quadrants 3 months after uneventful phacoemulsification and IOL implantation. These changes are accompanied by a significant fall in IOP in the short term.
Association Between Outbreaks of Highly Pathogenic Avian Influenza Subtype H5N1 and Migratory Waterfowl (Family Anatidae) Populations
Authors: Ward M. P. , Maftei D. N. , Apostu C. L. , Suru A. R.
Published: September 2008

Highly pathogenic avian influenza (HPAI) virus subtype H5N1 threatens poultry production and human health. Understanding the role that migratory waterfowl play in introducing and maintaining this infection is critical to control the outbreaks. A study was conducted to determine if the occurrence of HPAI subtype H5N1 outbreaks in village poultry in Romania, 2005–2006, was associated with proximity to populations of migratory waterfowl. Reported outbreaks – which could be grouped into three epidemic phases – and migratory waterfowl sites were mapped. The migratory waterfowl site closest to each outbreak was identified. The distances between outbreaks occurring in phase 1 and 2 of the epidemic and the closest migratory waterfowl site were significantly (P < 0.001) less than in phase 3, but these distances were only useful in predicting when outbreaks occurred during phase 1 (October–December, 2005) of the epidemic. A spatial lag (ρ = 0.408, P = 0.041) model best fit the data, using distance and [distance]*[distance] as predictors (R2 = 0.425). The correlation between when outbreaks were predicted to occur and when they were observed to occur was 0.55 (P = 0.006). Results support the hypothesis that HPAI virus subtype H5N1 infections of village poultry in Romania during the autumn of 2005 might have occurred via exposure to migratory populations of waterfowl.
Attenuation and Preserved Immunogenic Potential of Yersinia pseudotuberculosis Mutant Strains Evidenced in Oral Pig Model
Authors: Najdenski H. , Golkocheva‐Markova E. , Kussovski V. , Vesselinova A. , Garbom S. , Wolf‐Watz H.
Published: September 2008

Experimental oral infection of pigs with a parental Yersinia pseudotuberculosis strain pIB102, serotype O:3 and two mutant isogenic strains – pIB155,ΔyopK and pIB44,ΔypkA has been carried out. Clinical findings, microbiological and immunological parameters were examined in dynamics from day 7 to day 60 post‐infection (p.i.). All types of infections ran asymptomatically, without hyperthermia, loss of appetite, etc. Experiments on the blood parameters demonstrated a transient leucocytosis with lymphocytosis and monocytosis better expressed after yopK infection. Even though pig is usually known as a reservoir of yersiniae, bacterial colonization was found in mesenterial lymph nodes and tonsils on day 7, respectively 14 p.i. with parental strain, and only in tonsils on day 14 p.i. with both mutant strains. The augmented sensitivity of mutants to the bactericidal effect of leukocytes and blood sera is the characteristic feature of attenuation in their pathogenicity, compared to the parental strain. Comparative in vitro experiments on the immune response and immunostimulating capacity of Y. pseudotuberculosis mutant strains verify their preserved immunogenic potential, predominantly in case of yopK. Hyperplasia and strong activation of the lymph tissue of Peyer’s patches, mesenterial lymph nodes, tonsils and spleen of pigs challenged with both mutant strains were proved as immunomorphological rearrangements. The results obtained give the reason to claim that the genetically constructed yopK null mutant strain is significantly attenuated but is still immunogenic and has the potential for a live vaccine carrier strain.
Investigations into the Prevention of Neonatal Ancylostoma caninum Infections in Puppies by Application of Imidacloprid 10% Plus Moxidectin 2.5% Topical Solution to the Pregnant Dog
Authors: Krämer F. , Epe C. , Mencke N.
Published: September 2008

The aim of the investigation was to examine whether a single topical administration of a combination of imidacloprid and moxidectin to pregnant dogs could prevent neonatal infections with reactivated Ancylostoma caninum larvae. Three pregnant beagles, infected with A. caninum, were treated topically with the combination on day 56 of pregnancy. Three further dogs served as untreated controls. Treatment appeared to prevent neonatal infections in the puppies completely. Neither intestinal stages nor somatic larvae were found in two examined puppies per litter. All puppies and dams of the treatment group remained coproscopically negative. No side‐effects in dams or puppies were observed. Two of three untreated dams showed a patent infection after parturition. Necropsy of two puppies of each negative control litter revealed seven intestinal and five somatic A. caninum stages in total. One litter of the untreated dams showed a patent infection 33 days after parturition. In the other two litters, no representative sample sizes could be collected.
Anti-Polyribosylribitol Phosphate Antibody Concentrations and Avidities in Children since the Start ofHaemophilus influenzaeType b Immunization of Infants in the United Kingdom
Authors: Kelly Dominic F. , Moxon E. Richard , Yu Ly-Mee , Pollard Andrew J.
Published: September 2008

The introduction of routine infant immunization withHaemophilus influenzaetype b (Hib) conjugate vaccines in the United Kingdom in 1992 led to a significant reduction in invasive disease due to this organism. Subsequently, between 1999 and 2003 there was an increase in the number of immunized children with Hib infection. We investigated whether the rise in cases was related to changes in anti-polyribosylribitol phosphate (PRP) antibody concentration or avidity. Using stored sera, we analyzed temporal changes in antibody levels among 3- to 5-year-old children immunized between 1991 and 2000. Anti-PRP antibody concentrations were higher in 3- to 5-year-olds who received infant immunization in 1991 than those in subsequent years. This difference may be related to changes in either the mode of administration of Hib conjugate vaccines or the rates of Hib nasopharyngeal carriage. This study emphasizes the factors affecting anti-PRP antibody concentration following immunization with conjugate vaccines and the importance of these in long-term protection from invasive disease.
Immune Responses of Mice with Different Genetic Backgrounds to Improved Multiepitope, Multitarget Malaria Vaccine Candidate Antigen FALVAC-1A
Authors: Kaba S. A. , Price A. , Zhou Z. , Sundaram V. , Schnake P. , Goldman I. F. , Lal A. A. , Udhayakumar V. , Todd C. W.
Published: September 2008

FALVAC-1A is a second-generation multitarget, multiepitope synthetic candidate vaccine againstPlasmodium falciparum, incorporating elements designed to yield a stable and immunogenic molecule. Characteristics of the immunogenicity of FALVAC-1A were evaluated in congenic (H-2b, H-2k, andH-2d) and outbred strains of mice. The influences of four adjuvants (aluminum phosphate, QS-21, Montanide ISA-720, and copolymer CRL-1005) on different aspects of the immune response were also assessed. FALVAC-1A generated strong antibody responses in all mouse strains. The highest mean enzyme-linked immunosorbent assay (ELISA) antibody concentrations against FALVAC-1A were observed in the outbred ICR mice, followed by B10.BR, B10.D2, and C57BL/6 mice, though this order varied for the different adjuvants, with no statistical differences between mouse strains. In all mouse strains, the highest anti-FALVAC-1A antibody titers in ELISAs were induced by FALVAC-1A in copolymer and ISA-720 formulations, followed by QS-21 and AlPO4. These antibodies were of all four subclasses, though immunoglobulin G1 (IgG1) predominated, with the exception of FALVAC-1A with the QS-21 adjuvant, which induced predominantly IgG2c responses. Both sporozoites and blood stages ofP. falciparumwere recognized by anti-FALVAC-1A sera in the immunofluorescence assay. In addition to antibody, cellular immune responses were detected; these responses were studied by examining spleen cells producing gamma interferon and interleukin-4 in enzyme-linked immunospot assays. In summary, FALVAC-1A was found to be highly immunogenic and elicited functionally relevant antibodies that can recognize sporozoites and blood-stage parasites in diverse genetic backgrounds.
Phase I Study of a Herpes Simplex Virus Type 2 (HSV-2) DNA Vaccine Administered to Healthy, HSV-2-Seronegative Adults by a Needle-Free Injection System
Authors: Cattamanchi Ashok , Posavad Christine M. , Wald Anna , Baine Yaela , Moses Jennifer , Higgins Terry J. , Ginsberg Richard , Ciccarelli Richard , Corey Lawrence , Koelle David M.
Published: September 2008

We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 μg, 300 μg, 1,000 μg or 3,000 μg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-μg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 μg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.
Plastic Polymers for Efficient DNA Microarray Hybridization: Application to Microbiological Diagnostics
Authors: Zhao Zhengshan , Peytavi Régis , Diaz-Quijada Gerardo A. , Picard Francois J. , Huletsky Ann , Leblanc Éric , Frenette Johanne , Boivin Guy , Veres Teodor , Dumoulin Michel M. , Bergeron Michel G.
Published: September 2008

Fabrication of microarray devices using traditional glass slides is not easily adaptable to integration into microfluidic systems. There is thus a need for the development of polymeric materials showing a high hybridization signal-to-background ratio, enabling sensitive detection of microbial pathogens. We have developed such plastic supports suitable for highly sensitive DNA microarray hybridizations. The proof of concept of this microarray technology was done through the detection of four human respiratory viruses that were amplified and labeled with a fluorescent dye via a sensitive reverse transcriptase PCR (RT-PCR) assay. The performance of the microarray hybridization with plastic supports made of PMMA [poly(methylmethacrylate)]-VSUVT or Zeonor 1060R was compared to that with high-quality glass slide microarrays by using both passive and microfluidic hybridization systems. Specific hybridization signal-to-background ratios comparable to that obtained with high-quality commercial glass slides were achieved with both polymeric substrates. Microarray hybridizations demonstrated an analytical sensitivity equivalent to approximately 100 viral genome copies per RT-PCR, which is at least 100-fold higher than the sensitivities of previously reported DNA hybridizations on plastic supports. Testing of these plastic polymers using a microfluidic microarray hybridization platform also showed results that were comparable to those with glass supports. In conclusion, PMMA-VSUVT and Zeonor 1060R are both suitable for highly sensitive microarray hybridizations.