bluuebunny/crossref_metadata_2025 huggingface dataset:
Four Waves of Evaluation Diffusion
Authors: Vedung Evert
Published: July 2010

This article investigates the dissemination of evaluation as it appears from a Swedish and to a lesser extent an Atlantic vantage point since 1960. Four waves have deposited sediments, which form present-day evaluative activities. The scientific wave entailed that academics should test, through two-group experimentation, appropriate means to reach externally set, admittedly subjective, goals. Public decision-makers were then supposed to roll out the most effective means. Faith in scientific evaluation eroded in the early 1970s. It has since been argued that evaluation should be participatory and non-experimental, with information being elicited from users, operators, managers and other stakeholders through discussions. In this way, the dialogue-oriented wave entered the scene. Then the neo-liberal wave from around 1980 pushed for market orientation. Deregulation, privatization, contracting-out, efficiency and customer influence became key phrases. Evaluation as accountability, value for money and customer satisfaction was recommended. Under the slogan ‘What matters is what works’ the evidence-based wave implies a renaissance for scientific experimentation.
Starting age and L1 and L2 interaction
Authors: Mihaljević Djigunović Jelena
Published: July 2010

The study looks into the multi-competence of early and late beginners by studying the interaction of achievement in their L1 and L2. In the context of this study L1 was Croatian and L2 English. Early beginners are defined as learners who started learning English before age 10 and late beginners as learners who started at 10 or later. The findings of this study show that the multi-competence of early and later beginners differs in terms of interaction between their L1 and L2. It is suggested that early beginners, through their longer exposure to L2, reach the necessary competence levels in their two languages sooner to allow transfer in both directions. Before these levels are reached, L1—L2 interactions are either non-existent or weak.
Development of the Oxford Hills Healthy Moms Project Using a Social Marketing Process: A Community-Based Physical Activity and Nutrition Intervention for Low-Socioeconomic-Status Mothers in a Rural Area in Maine
Authors: Dharod Jigna M. , Drewette-Card Rebecca , Crawford David
Published: July 2010

A physical activity and nutrition community intervention called the Oxford Hills Healthy Moms (OHHM) Project was developed using a multifaceted social marketing process, including review of state surveillance results, key informant interviews, and a survey and focus group discussions with low-socioeconomic-status (low-SES) mothers. This formative work was used to make key decisions on the selection of the intervention region, segmentation of the audience, and design of intervention strategies addressing multiple levels of the socioecological model. The OHHM Project aims to increase fruit and vegetable consumption and physical activity levels among low-SES mothers in the Oxford Hills region of Maine. The OHHM Project includes five components: (a) physical activity buddy program, (b) cooking club with education, (c) fruit and vegetable discount buying club with education, (d) increased access to produce vendors, and (e) increased access to places for physical activity.
Dorsal Dimelia: Report of Two Cases With an Emphasis On the Variation of Phenotypic Expression and a Search for Candidate Causative Genes
Authors: Al-Qattan M.M. , Almazyad M. , Shamseldin H. , Alkuraya F.S.
Published: July 2010

Dorsal dimelia is a form of duplication along the dorsoventral axis of the developing limb. Previous authors reporting on this rare entity have stated that the essential feature of the deformity is the presence of double or circumferential nail at the tip of the finger and that the aetiology is probably related to a mutation of Engrailed-1 (En-1). In this paper we report on two cases to demonstrate that the deformity in humans may be fully or partially expressed, with or without the double nail deformity, respectively. We also reviewed reported cases in humans and experimental animals and searched our two cases for candidate causative genes within the En-1 pathway.
Chemopreventive effects of Coltect, a novel dietary supplement, alone and in combination with 5-aminosalicylic acid in 1,2-dimethylhydrazine-induced colon cancer in rats
Authors: Aroch Ilan , Kraus Sarah , Naumov Inna , Ron Ehud , Shapira Shiran , Kazanov Dina , Giladi Nis , Litvak Alex , Lev-Ari Shahar , Hallak Aharon , Dotan Iris , Shpitz Baruch , Arber Nadir
Published: July 2010

Objectives: Coltect is a novel dietary supplement containing curcumin, green tea and selenomethionine. Previous reports have suggested that these agents can prevent colorectal cancer (CRC). The present study examined the chemopreventive effect of Coltect alone or combined with 5-aminosalicylic acid (5-ASA) using the 1,2-dimethylhydrazine (DMH) model in rats.

Methods: The effect of Coltect was examined on HT-29 CRC cells by growth inhibition assay. Apoptosis was determined by annexin V-FITC/PI staining. Male rats were injected with DMH in vivo and treated with Coltect 150 mg/kg, 5-ASA 50 mg/kg or their combination, by oral gavage. Aberrant crypt foci (ACF) were identified by methylene blue staining.

Results: HT-29 cells exhibited a dose-dependent response to Coltect. Part of the growth inhibition can be explained by the induction of mild-moderate apoptosis in cancer cells (28%) compared with the untreated cells (10%). In the in vivo model, the average number of ACF was divided into small (1-3 crypts) or large (≥4 crypts). The Coltect compound reduced the number of small and large ACF similarly to 5-ASA (40% reduction). This reduction was amplified by combining the two agents (70% reduction).

Conclusion: Coltect inhibits the growth of colon cancer cells, induces apoptosis and inhibits ACF development. Furthermore, it augments the growth inhibitory effect of 5-ASA in vivo. This may be clinically important since this safe dietary supplement-drug combination can be administered as a chemopreventive regimen for the treatment of CRC.
Study on microstructure of squeeze casting AZ91D alloy
Authors: Yang Y. L. , Peng L. M. , Fu P. H. , Hu B. , Ding W. J.
Published: July 2010

The present paper reports the investigation of the microstructure distribution of squeeze cast AZ91D alloy. The microstructure of squeeze cast AZ91D alloy is not uniform and is composed of four zones, which are chilled layer, segregation zone, pressured crystallisation area and hot spot area respectively. Moreover, in the pressured crystallisation area, the microstructure sequence in the transverse section from the outside to the inside could be divided into four sublayers, such as fine equiaxial dendrite area, dendrite area with a high directivity, confusion dendrite area and disorder dendrite area. The volume fraction of the intermetallic compound Mg17Al12 also varied with the location. The volume fraction of Mg17Al12 in the pressured crystallisation area is the largest except in the segregated zone.
Degassing of magnesium alloy by rotating impeller degasser Part 2 – effect on microstructure and mechanical properties
Authors: Zhang E. , Wang G. J. , Hu Z. C.
Published: July 2010

Magnesium alloy shows great potential application in automatic industry. In production practice, recycled magnesium alloys are normally used in order to reduce the production costs. In this work, a rotary impeller was used to degas AZ91 magnesium alloy with 10 wt-% recycled alloy in order to investigate the effect of degassing on mechanical properties. Microstructure and fracture surface of AZ91 samples with and without degassing were observed by SEM to reveal the control mechanism. Mechanical properties measurements have shown that degassing significantly increased the tensile strength and especially the elongation of the as cast magnesium alloy. Microstructure and fracture surface observation indicated that high hydrogen content resulted in an increase in shrinkage in magnesium casting, which contributes to low mechanical properties. Casting condition also affected the influence of hydrogen content on the mechanical properties. High increase in strength and elongation was observed in the permanent and the low pressure sand magnesium castings by reducing hydrogen content. It has been shown that rotary degassing as a degassing technology exhibits high degassing efficiency to magnesium melt.
Chemistry, morphology and structural characteristics of synthetic Al-lizardite
Authors: Bentabol M. , Ruiz Cruz M. D. , Sobrados I.
Published: July 2010

Al-lizardite has been synthesized under hydrothermal conditions (200ºC). Morphologically, Al-lizardite consists of thin platy particles ~400 Å wide and ~150 Å thick. Structurally, the X-ray diffraction patterns indicate that the 2H2 polytype is dominant, with cell parameters: a = 5.311(0.006) Å; c = 14.333 (0.013) Å and space group P63. High-resolution transmission electron microscopy images revealed, however, the presence of other polytypes and abundant stacking disorder. Chemically, Al-lizardite consists of a single population with average tetrahedral composition Si1.74Al0.26. In contrast to previously described Al-rich serpentines (amesite and Al-lizardite), this Al-lizardite is characterized by an asymmetrical Al distribution, with VIAl ≈0.70 and IVAl ≈0.25 atoms per formula unit.
XRF and nitrogen adsorption studies of acid-activated palygorskite
Authors: Zhang Junping , Wang Qin , Chen Hao , Wang Aiqin
Published: July 2010

The effects of acid activation on the chemical composition, surface area and pore structure of palygorskite from Xuyi (Jiangsu, P.R. China) were investigated systematically using X-ray fluorescence (XRF) and BET techniques. The palygorskite samples were activated with HCl, H2SO4 and H3PO4 of various concentrations at 80ºC for 4 h. The influences of acid concentration and acid type on the chemical composition, adsorption-desorption isotherms at 77 K, pore-size distribution, surface area and pore volume were studied in detail. The contents of most components of palygorskite decrease with increasing acid concentration except for Si and Ti. HCl shows a greater activation activity and its effect on the dissolution of components of palygorskite is greater than that of H2SO4 and H3PO4. It was found that 3 mol l–1 H3PO4 is a more efficient activator for increasing the number of micropores in palygorskite, whereas 12 mol l–1 HCl is more suitable for use in enhancing the number of meso- and macropores. The acid concentration and acid type have a great influence on the surface area and pore volume. HCl is the most effective at enhancing the external surface area and mesopore volume of palygorskite, whereas, H3PO4 is more suitable for use in improving the micropore surface and volume.
Statistical analysis of geochemical data: a tool for discriminating between kaolin deposits of hypogene and supergene origin, Patagonia, Argentina
Authors: Cravero F. , Marfil S. A. , Maiza P. J.
Published: July 2010

The numerous kaolin deposits located in Patagonia, Argentina, have been formed by hypogene or supergene processes. The primary origin has been established from O18 and D isotopic composition of the main minerals, kaolinite and/or dickite, and from the behaviour of certain elements during the alteration. The aim of this paper was to find if there is a tool, other than oxygen-deuterium data, to establish the origin of the Patagonian kaolin deposits. To handle the large number of variables per sample, a statistical multivariate study was used. The Principal Component method defines, on one hand the variables that better characterize each deposit and, on the other hand, the correlation between them. Fifty seven elements were considered and those that were not explained using these two components (which represent 75% of the total variance of the model) were discarded. As a result, the contents of Fe2O3, P2O5, LOI, Sr, Y, Zr, V, Pb, Hf, Rb, S and REE were used and the results show that the two components separate the deposits into two fields that are consistent with the process of formation. The first component indicates that Fe2O3, Y, Rb, U and HREE are more abundant in the supergene deposits, whereas, Sr, Pb, S and V are more abundant in the hypogene deposits. The second component shows that S, P2O5 and the LREE are enriched in the hydrothermal deposits, whereas Zr is more abundant in those formed under weathering conditions.
Bendadaite, a new iron arsenate mineral of the arthurite group
Authors: Kolitsch U. , Atencio D. , Chukanov N. V. , Zubkova N. V. , Menezes Filho L. A. D. , Coutinho J. M. V. , Birch W. D. , Schlüter J. , Pohl D. , Kampf A. R. , Steele I. M. , Favreau G. , Nasdala L. , Möckel S. , Giester G. , Pushcharovsky D. Yu.
Published: July 2010

Bendadaite, ideally Fe2+Fe23+ (AsO4)2(OH)2·4H2O, is a new member of the arthurite group. It was found as a weathering product of arsenopyrite on a single hand specimen from the phosphate pegmatite Bendada, central Portugal (type locality). Co-type locality is the granite pegmatite of Lavra do Almerindo (Almerindo mine), Linópolis, Divino das Laranjeiras county, Minas Gerais, Brazil. Further localities are the Veta Negra mine, Copiapó province, Chile; Oumlil-East, Bou Azzer district, Morocco; and Pira Inferida yard, Fenugu Sibiri mine, Gonnosfanadiga, Medio Campidano Province, Sardinia, Italy.

Type bendadaite occurs as blackish green to dark brownish tufts (<0.1 mm long) and flattened radiating aggregates, in intimate association with an intermediate member of the scorodite–mansfieldite series. It is monoclinic, space group P21/c, with a = 10.239(3) Å, b = 9.713(2) Å, c = 5.552(2) Å, β = 94.11(2)°, V = 550.7(2) Å3, Z = 2. Electron-microprobe analysis yielded (wt.%): CaO 0.04, MnO 0.03, CuO 0.06, ZnO 0.04, Fe2O3 (total) 43.92, Al2O3 1.15, SnO2 0.10, As2O5 43.27, P2O5 1.86, SO3 0.03. The empirical formula is (Fe2+0.52Fe3+0.32☐0.16)Σ1.00(Fe3+1.89Al0.11)Σ2.00(As1.87P0.13)Σ2.00O8(OH)2.00·4H2O based on 2(As,P) and assuming ideal 8O, 2(OH), 4H2O and complete occupancy of the ferric iron site by Fe3+ and Al. Optically, bendadaite is biaxial, positive, 2Vest. = 85±4°, 2Vcalc. = 88°, with α 1.734(3), β 1.759(3), γ 1.787(4). Pleochroism is medium strong: X pale reddish brown, Y yellowish brown, Z dark yellowish brown; absorption Z > Y > X, optical dispersion weak, r > v. Optical axis plane is parallel to (010), with X approximately parallel to a and Z nearly parallel to c. Bendadaite has vitreous to sub-adamantine luster, is translucent and non-fluorescent. It is brittle, shows irregular fracture and a good cleavage parallel to {010}. Dmeas. 3.15±0.10 g/cm3, Dcalc. 3.193 g/cm3 (for the empirical formula). The five strongest powder diffraction lines [d in Å (I)(hkl)] are 10.22 (10)(100), 7.036 (8)(110), 4.250 (5)(111), 2.865 (4)(), 4.833 (3)(020,011). The d spacings are very similar to those of its Zn analogue, ojuelaite. The crystal structure of bendadaite was solved and refined using a crystal from the co-type locality with the composition (Fe2+0.95☐0.05)Σ1.00(Fe3+1.80Al0.20)Σ2.00(As1.48P0.52)Σ2.00O8(OH)2·4H2O (R = 1.6%), and confirms an arthurite-type atomic arrangement.
The structure of H3O+-exchanged pharmacosiderite
Authors: Mills S. J. , Hager S. L. , Leverett P. , Williams P. A. , Raudsepp M.
Published: July 2010

The crystal structure of H3O+-exchanged pharmacosiderite (pharmacosiderite is KFe4(AsO4)3(OH)4·nH2O, sensu stricto) has been determined by single-crystal X-ray diffraction and refined to R1 = 0.0418. H3O+-exchanged pharmacosiderite, (H3O+)Fe4(AsO4)3(OH)4·4.5H2O, is cubic, space group Pm, with a = 7.982(9) Å, V = 508.5(9) Å3 and Z = 1. The structure broadly conforms to that of the general pharmacosiderite structure type, with the hydronium ion generated by partial protonation of a site corresponding to a molecule of water of crystallization and its symmetry-related equivalents. In addition, the structure of a “pharmacosiderite” from Cornwall, United Kingdom, in which no alkali metals could be detected, has been re-evaluated and found to be consistent with that of the H3O+- exchanged structure. Its composition is (H3O+)Fe4(AsO4)3(OH)4·4H2O, with the partially occupied water found for the exchanged structure at (½, ½, ½) being absent in this case.
The crystal structure of zigrasite, MgZr(PO4)2(H2O)4, a heteropolyhedral framework structure
Authors: Hawthorne F. C. , Simmons W. B.
Published: July 2010

The crystal structure of zigrasite, ideally MgZr(PO4)2(H2O)4, a 5.3049(2), b 9.3372(4), c 9.6282(5) Å, α 97.348(1)°, β 91.534(1)°, γ 90.512(4)°, V 472.79(5) Å3, Z = 2, triclinic, P1, Dcalc. 2.66 g.cm–3, from the giant 1972 pocket at Newry, Oxford County, Maine, USA, has been solved and refined to R1 3.75% on the basis of 2623 unique reflections (Fo > 4σF). There are two P sites, each of which is solely occupied by P with  distances of 1.532 and 1.533 Å, respectively. There are two Mg sites, both of which are occupied by Mg and are octahedrally coordinated two O anions and four (H2O) groups with  distances of 2.064 and 2.075 Å, respectively. There is one Zr site, occupied by Zr and octahedrally coordinated by six O anions with a  distance of 2.065 Å . The (ZrO6) octahedron shares corners with six (PO4) tetrahedra, forminga [Zr(PO4)2] sheet parallel to (001). These sheets are stacked in the c direction and linked by (MgO2(H2O)4) octahedra that share O atoms with the (PO4) groups. The structure is formally a heteropolyhedral framework structure, but the linkage is weaker in the c direction, accounting for the marked (001) cleavage.
Determining gene flow and the influence of selection across the equatorial barrier of the East Pacific Rise in the tube-dwelling polychaete Alvinella pompejana
Authors: Plouviez Sophie , Le Guen Dominique , Lecompte Odile , Lallier François H , Jollivet Didier
Published: July 2010

Background

Comparative phylogeography recently performed on the mitochondrialcytochrome oxidase I(mtCOI) gene from seven deep-sea vent species suggested that the East Pacific Rise fauna has undergone a vicariant event with the emergence of a north/south physical barrier at the Equator 1-2 Mya. Within this specialised fauna, the tube-dwelling polychaeteAlvinella pompejanashowed reciprocal monophyly atmtCOIon each side of the Equator (9°50'N/7°25'S), suggesting potential, ongoing allopatric speciation. However, the development of a barrier to gene flow is a long and complex process. Secondary contact between previously isolated populations can occur when physical isolation has not persisted long enough to result in reproductive isolation between genetically divergent lineages, potentially leading to hybridisation and subsequent allelic introgression. The present study evaluates the strength of the equatorial barrier to gene flow and tests for potential secondary contact zones betweenA. pompejanapopulations by comparing themtCOIgene with nuclear genes.

Results

Allozyme frequencies and the analysis of nucleotide polymorphisms at three nuclear loci confirmed the north/south genetic differentiation ofAlvinella pompejanapopulations along the East Pacific Rise. Migration was oriented north-to-south with a moderate allelic introgression between the two geographic groups over a narrow geographic range just south of the barrier. Multilocus analysis also indicated that southern populations have undergone demographic expansion as previously suggested by a multispecies approach. A strong shift in allozyme frequencies together with a high level of divergence between alleles and a low number of 'hybrid' individuals were observed between the northern and southern groups using thephosphoglucomutasegene. In contrast, theS-adenosylhomocysteine hydrolasegene exhibited reduced diversity and a lack of population differentiation possibly due to a selective sweep or hitch-hiking.

Conclusions

The equatorial barrier leading to the separation of East Pacific Rise vent fauna into two distinct geographic groups is still permeable to migration, with a probable north-to-south migration route forA. pompejana. This separation also coincides with demographic expansion in the southern East Pacific Rise. Our results suggest that allopatry resulting from ridge offsetting is a common mechanism of speciation for deep-sea hydrothermal vent organisms.
A genetic dissection of breed composition and performance enhancement in the Alaskan sled dog
Authors: Huson Heather J , Parker Heidi G , Runstadler Jonathan , Ostrander Elaine A
Published: July 2010

Background

The Alaskan sled dog offers a rare opportunity to investigate the development of a dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled dog lines, and in doing so, determined the breed origins of specific performance-related behaviors.

One hundred and ninety-nine Alaskan sled dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped purebred dog breeds. Sled dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure.

Results

We observe that the Alaskan sled dog has a unique molecular signature and that the genetic profile is sufficient for identifying dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic.

Conclusion

We have established a genetic breed profile for the Alaskan sled dog, identified profile variance between sprint and distance dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled dog.
Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse
Authors: Chadi Sead , Young Rachel , Le Guillou Sandrine , Tilly Gaëlle , Bitton Frédérique , Martin-Magniette Marie-Laure , Soubigou-Taconnat Ludivine , Balzergue Sandrine , Vilotte Marthe , Peyre Coralie , Passet Bruno , Béringue Vincent , Renou Jean-Pierre , Le Provost Fabienne , Laude Hubert , Vilotte Jean-Luc
Published: July 2010

Background

The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages.

Results

Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences.

Conclusions

These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.
p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance
Authors: Yang Ji Yeon , Ha Seon-Ah , Yang Yun-Sik , Kim Jin Woo
Published: July 2010

Background

Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells.

Methods

Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated.

Results

YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics.

Conclusion

Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists.
Antibacterial properties of tualang honey and its effect in burn wound management: a comparative study
Authors: Nasir Nur-Azida Mohd , Halim Ahmad Sukari , Singh Kirnpal-Kaur Banga , Dorai Ananda Aravazhi , Haneef Mehru-Nisha Muhammad
Published: July 2010

Background

The use of honey as a natural product of Apis spp. for burn treatment has been widely applied for centuries. Tualang honey has been reported to have antibacterial properties against various microorganisms, including those from burn-related diagnoses, and is cheaper and easier to be absorbed by Aquacel dressing. The aim of this study is to evaluate the potential antibacterial properties of tualang honey dressing and to determine its effectiveness as a partial thickness burn wound dressing.

Methods

In order to quantitate the bioburden of the swabs, pour plates were performed to obtain the colony count (CFU/ml). Swabs obtained from burn wounds were streaked on blood agar and MacConkey agar for bacterial isolation and identification. Later, antibacterial activity of Aquacel-tualang honey, Aquacel-Manuka honey, Aquacel-Ag and Aquacel- plain dressings against bacteria isolated from patients were tested (in-vitro) to see the effectiveness of those dressings by zone of inhibition assays.

Results

Seven organisms were isolated. Four types of Gram-negative bacteria, namely Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas spp. and Acinetobacter spp., and three Gram-positive bacteria, namely Staphylococcus aureus, coagulase-negative Staphylococcus aureus (CONS) and Streptococcus spp., were isolated. Total bacterial count decreased on day 6 and onwards. In the in-vitro antibacterial study, Aquacel-Ag and Aquacel-Manuka honey dressings gave better zone of inhibition for Gram positive bacteria compared to Aquacel-Tualang honey dressing. However, comparable results were obtained against Gram negative bacteria tested with Aquacel-Manuka honey and Aquacel-Tualang honey dressing.

Conclusions

Tualang honey has a bactericidal as well as bacteriostatic effect. It is useful as a dressing, as it is easier to apply and is less sticky compared to Manuka honey. However, for Gram positive bacteria, tualang honey is not as effective as usual care products such as silver-based dressing or medical grade honey dressing.
Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition
Authors: Caffarel María M , Andradas Clara , Mira Emilia , Pérez-Gómez Eduardo , Cerutti Camilla , Moreno-Bueno Gema , Flores Juana M , García-Real Isabel , Palacios José , Mañes Santos , Guzmán Manuel , Sánchez Cristina
Published: July 2010

Background

ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors.

Results

Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2.

Conclusions

Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.
Copy number and gene expression differences between African American and Caucasian American prostate cancer
Authors: Rose Amy E , Satagopan Jaya M , Oddoux Carole , Zhou Qin , Xu Ruliang , Olshen Adam B , Yu Jessie Z , Dash Atreya , Jean-Gilles Jerome , Reuter Victor , Gerald William L , Lee Peng , Osman Iman
Published: July 2010

Background

The goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach.

Methods

AA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K).

Results

BAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fisher's exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response.

Conclusions

Our data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.
Effect of abrupt weaning at housing on leukocyte distribution, functional activity of neutrophils, and acute phase protein response of beef calves
Authors: Lynch EM , Earley B , McGee M , Doyle S
Published: July 2010

Background

Sixteen, spring-born, single suckled, castrated male calves of Limousin × Holstein-Friesian and Simmental × Holstein-Friesian dams respectively, were used to investigate the effect of weaning on total leukocyte and differential counts, neutrophil functional activity, lymphocyte immunophenotypes, and acute phase protein response. Calves grazed with their dams until the end of the grazing season when they were housed in a slatted floor shed. On the day of housing, calves were assigned to a treatment, (i) abruptly weaned (W:n= 8) or (ii) non-weaned (controls) (C:n= 8). Weaned calves were housed in pens without their dams, whereas non-weaned (control) calves were housed with their dams. Blood was collected on day -7, 0 (housing), 2, 7, and 14 to determine total leukocyte and differential counts and concentration of fibrinogen and haptoglobin. Lymphocyte immunophenotypes were characterised using selected surface antigens (CD4+, CD8+, WC1+(γδ T cells), MHC Class II+lymphocytes), and the functional activities of neutrophils (surface expression of L-selectin (CD62L), phagocytic and oxidative burst activity) were investigated using flow cytometry.

Results

Treatment × sampling time interactions (P< 0.05) were detected for total leukocyte and neutrophil counts, all lymphocyte subsets, mean fluorescence intensity of CD62L+neutrophils, and percentage neutrophils performing phagocytosis. On d 2, total leukocyte and neutrophil count increased (P< 0.001), and percentage CD4+and CD8+lymphocytes, percentage phagocytic neutrophils, mean fluorescence intensity of CD62L+neutrophils decreased (P< 0.05) in W compared with baseline (d 0), whereas they were unchanged (P> 0.05) in C. On d 2, percentage WC1+lymphocytes decreased (P< 0.05), whereas percentage MHC class II+lymphocytes increased (P< 0.05) in W and C, however the magnitude of change was greater in W than C. There were no treatment × sampling time interactions (P> 0.05) for monocyte, eosinophil, and basophil counts, percentage G1+neutrophils, or percentage oxidative burst positive neutrophils.

Conclusions

Abrupt weaning resulted in increased neutrophil counts and impaired trafficking and phagocytic function. Together with the changes in lymphocyte subsets, the results suggest that there was a greater transitory reduction in immune function at housing in abruptly weaned than non-weaned beef calves.
The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells
Authors: Ikeda Hirokuni , Taira Naruto , Hara Fumikata , Fujita Takeo , Yamamoto Hiromasa , Soh Junichi , Toyooka Shinichi , Nogami Tomohiro , Shien Tadahiko , Doihara Hiroyoshi , Miyoshi Shinichiro
Published: July 2010

Introduction

Microtubule-associated protein tau (MAPT) inhibits the function of taxanes and high expression of MAPT decreases the sensitivity to taxanes. The relationship between estrogen receptor (ER) and MAPT in breast cancer is unclear. In this study, we examined the correlation of MAPT expression with the sensitivity of human breast cancer cells to taxanes, and the relationship between ER and MAPT.

Methods

The correlation between MAPT expression and sensitivity to taxanes was investigated in 12 human breast cancer cell lines. Alterations in cellular sensitivity to taxanes were evaluated after knockdown of MAPT expression. ER expression was knocked down or stimulated in MAPT- and ER-positive cell lines to examine the relationship between ER and MAPT. The cells were also treated with hormone drugs (tamoxifen and fulvestrant) and taxanes.

Results

mRNA expression of MAPT did not correlate with sensitivity to taxanes. However, expression of MAPT protein isoforms of less than 70 kDa was correlated with a low sensitivity to taxanes. Downregulation of MAPT increased cellular sensitivity to taxanes. MAPT protein expression was increased by stimulation with 17-β-estradiol or tamoxifen, but decreased by ER downregulation and by fulvestrant, an ER inhibitor. The combination of fulvestrant with taxanes had a synergistic effect, whereas tamoxifen and taxanes had an antagonistic effect.

Conclusions

Expression of MAPT protein isoforms of less than 70 kDa is correlated with a low sensitivity to taxanes in breast cancer cells. ER influences MAPT expression and fulvestrant increases the sensitivity to taxanes in MAPT- and ER-positive breast cancer cells.
17β-Estradiol Rapidly Increases KATP Activity in GnRH via a Protein Kinase Signaling Pathway
Authors: Zhang Chunguang , Kelly Martin J. , Rønnekleiv Oline K.
Published: July 2010

17β-Estradiol (E2) both inhibits and excites GnRH neurons via presynaptic as well as postsynaptic mechanisms. Although it has been demonstrated that E2 can alter the excitability of GnRH neurons via direct actions, the intracellular signaling cascades mediating these actions are not well understood. Previously we have shown that the activity of one of the critical ion channels needed for maintaining GnRH neurons in a hyperpolarized state, the ATP-sensitive potassium channel (KATP) channel, is augmented by E2 in ovariectomized females. However, the mRNA expression of the KATP channel subunits Kir6.2 and SUR1 are unchanged with in vivo E2 treatment. Therefore, to elucidate the cellular signaling mechanism(s) modulating the channel activity, we did whole-cell patch-clamp recording of enhanced green fluorescent protein-GnRH neurons from ovariectomized female mice to study the acute effects of E2. E2 dose-dependently (EC50 = 0.6 nM) enhanced the diazoxide (channel opener)-activated KATP channel currents by 1.2- to 2.0-fold, which was antagonized by ICI 182,780. E2-BSA was equally as effective as E2, whereas E2 had no effect. The protein kinase A (PKA) activator forskolin mimicked the effects of E2, whereas the PKA inhibitor H89 and the protein kinase C (PKC) inhibitor bisindolylmaleimide I blocked the effects of E2. Similar to E2, STX, a membrane estrogen receptor (ER) agonist that does not bind to ERα or ERβ, also potentiated the diazoxide-induced KATP channel current by 1.5-fold. Therefore, E2 can potentiate KATP channel activity in GnRH neurons through a membrane ER-activated PKC-PKA signaling pathway.
Curcumin Protects Hepatic Stellate Cells against Leptin-Induced Activation in Vitro by Accumulating Intracellular Lipids
Authors: Tang Youcai , Chen Anping
Published: July 2010

Obesity and type II diabetes mellitus are often associated with hyperleptinemia and commonly accompanied by nonalcoholic steatohepatitis, which could cause hepatic fibrosis. During hepatic fibrogenesis, the major effectors hepatic stellate cells (HSCs) become active, coupling with depletion of cellular lipid droplets and downexpression of genes relevant to lipid accumulation. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit HSC activation. We recently reported that leptin stimulated HSC activation, which was eliminated by curcumin, a phytochemical from turmeric. The current study was designed to explore the underlying mechanisms, focusing on their effects on the level of intracellular lipids. We hypothesized that one of the mechanisms by which leptin stimulated HSC activation was to stimulate the depletion of intracellular lipids, which could be abrogated by curcumin by inducing expression of genes relevant to lipid accumulation. In this report, we observed that leptin dose dependently reduced levels of intracellular fatty acids and triglycerides in passaged HSCs, which were eliminated by curcumin. The phytochemical abrogated the impact of leptin on inhibiting the activity of AMP-activated protein kinase (AMPK) in HSCs in vitro. The activation of AMPK resulted in inducing expression of genes relevant to lipid accumulation and increasing intracellular lipids in HSCs in vitro. In summary, curcumin eliminated stimulatory effects of leptin on HSC activation and increased AMPK activity, leading to inducing expression of genes relevant to lipid accumulation and elevating the level of intracellular lipids. These results provide novel insights into mechanisms of curcumin in inhibiting leptin-induced HSC activation.
Differential Regulation of Plasma Obestatin and Ghrelin by Meal Intake and the Cholinergic System in Lean, But Not Obese Individuals
Authors: Maier Christina , Riedl Michaela , Vila Greisa , Wolzt Michael , Clodi Martin , Ludvik Bernhard , Luger Anton
Published: July 2010

Context: Obestatin is cosecreted with and stemming from the same precursor as ghrelin and is apparently involved in energy metabolism. Relatively little is known about the regulation of obestatin release.

Objective: The regulation of obestatin release and obestatin-to-ghrelin ratios by meal intake and the cholinergic system were studied in lean and obese subjects.

Design, Participants, and Setting: We conducted a randomized, double-blind, placebo-controlled, crossover study with 4 study days in eight obese (body mass index >30 kg/m2) and eight matched lean (body mass index <25 kg/m2) healthy subjects (two males and six females per group) at a University Clinical Research Unit.

Interventions: Atropine (1 mg iv) was administered alone and in combination with breakfast (550 kcal) intake, or placebo (isotonic saline) alone and in combination with breakfast.

Main Outcome Measures: We measured plasma obestatin and obestatin/ghrelin ratios.

Results: Both obestatin and ghrelin/obestatin ratios decreased significantly from baseline by either atropine or meal intake in lean individuals, with the two effects adding up on the combined atropine/breakfast day. In contrast, there were no statistically significant differences in obese subjects, who also showed significantly greater association between ghrelin and obestatin values than their lean counterparts.

Conclusions: Obestatin and ghrelin release is differentially regulated by meal intake and the cholinergic system in lean individuals. This regulation is impaired in obesity.
Tumor-Induced Hypophosphatemic Rickets in an Adolescent Boy—Clinical Presentation, Diagnosis, and Histological Findings in Growth Plate and Muscle Tissue
Authors: Haeusler G. , Freilinger M. , Dominkus M. , Egerbacher M. , Amann G. , Kolb A. , Schlegel W. , Raimann A. , Staudenherz A.
Published: July 2010

Context: The mechanism behind disabling muscle weakness in tumor-induced hypophosphatemic rickets is obscure. Histological investigation of growth plate tissue of patients with tumor-induced osteomalacia has so far not been reported.

Patient: A mesenchymal tumor was detected in the left distal fibula by 68Ga-DOTATOC in a 17-yr-old boy with adolescent onset of severe hypophosphatemic rickets. Disabling muscle weakness improved within days after surgery, and normal mobility was restored within months.

Methods and Results: The resected tissue included part of the growth plate allowing immunohistochemical investigation. Positive staining of FGF23 was found in the tumor cells and in hypertrophic chondrocytes, osteoblasts, and osteoclasts of the adjacent growth plate. This distribution matched that found in growth plate tissue of a healthy control. We found positive staining for the somatostatin receptor not only in the tumor but also within the growth plate and adjacent bony tissue in the patient and the healthy control. Muscle tissue provided evidence for a partial defect in respiratory chain complexes I-IV. Biochemical markers were nearly or completely restored to normal 12 months after surgery.

Conclusions: Hypertrophic growth plate chondrocytes are a target or source of FGF23 in tumor-induced osteomalacia. Low serum phosphate, FGF23, or other factors produced by the tumor may interfere with mitochondrial function.
Discovery of Glucocorticoid Receptor-β in Mice with a Role in Metabolism
Authors: Hinds Terry D. , Ramakrishnan Sadeesh , Cash Harrison A. , Stechschulte Lance A. , Heinrich Garrett , Najjar Sonia M. , Sanchez Edwin R.
Published: July 2010

Glucocorticoid hormones control diverse physiological processes, including metabolism and immunity, by activating the major glucocorticoid receptor (GR) isoform, GRα. However, humans express an alternative isoform, human (h)GRβ, that acts as an inhibitor of hGRα to produce a state of glucocorticoid resistance. Indeed, evidence exists that hGRβ contributes to many diseases and resistance to glucocorticoid hormone therapy. However, rigorous testing of the GRβ contribution has not been possible, because rodents, especially mice, are not thought to express the β-isoform. Here, we report expression of GRβ mRNA and protein in the mouse. The mGRβ isoform arises from a distinct alternative splicing mechanism utilizing intron 8, rather than exon 9 as in humans. The splicing event produces a form of β that is similar in structure and functionality to hGRβ. Mouse (m)GRβ has a degenerate C-terminal region that is the same size as hGRβ. Using a variety of newly developed tools, such as a mGRβ-specific antibody and constructs for overexpression and short hairpin RNA knockdown, we demonstrate that mGRβ cannot bind dexamethasone agonist, is inhibitory of mGRα, and is up-regulated by inflammatory signals. These properties are the same as reported for hGRβ. Additionally, novel data is presented that mGRβ is involved in metabolism. When murine tissue culture cells are treated with insulin, no effect on mGRα expression was observed, but GRβ was elevated. In mice subjected to fasting-refeeding, a large increase of GRβ was seen in the liver, whereas mGRα was unchanged. This work uncovers the much-needed rodent model of GRβ for investigations of physiology and disease.