bluuebunny/crossref_metadata_2025_split huggingface dataset:
No association of the polymorphisms of the frizzled-related protein gene with peak bone mineral density in Chinese nuclear families
Authors: Gao Gao , Zhang Zhen-Lin , He Jin-Wei , Zhang Hao , Yue Hua , Hu Wei-Wei , Gu Jie-Mei , Fu Wen-Zhen , Hu Yun-Qiu , Li Miao , Liu Yu-Juan , Yu Jin-Bo 
Published: January 2010

Abstract

Background
The Wnt/beta-catenin signaling pathway plays an important role in skeletal development. Polymorphisms of frizzled-related protein (FRZB), an antagonist of this pathway, may generate variations in bone mineral density (BMD). In this study, we analyzed the association between FRZB genotypes and peak BMD variation in the spines and hips of two relatively large samples of Chinese female-offspring and male-offspring nuclear families.

Methods
We recruited 1,260 subjects from 401 female-offspring nuclear families and 1,296 subjects from 427 male-offspring nuclear families and genotyped four tagging single nucleotide polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip osteoarthritis, were not selected in this study because of their low minor allele frequencies (MAFs) in Chinese people. The quantitative transmission disequilibrium test (QTDT) was used to analyze the association between each SNP and haplotype with peak BMD in female- and male-offspring nuclear families.

Results
In the female-offspring nuclear families, we found no evidence of an association between either single SNPs or haplotypes and peak BMD in the spine or hip. In the male-offspring nuclear families, no within-family association was observed for either SNPs or haplotypes, although a significant total association was found between rs4666865 and spine BMD (P = 0.0299).

Conclusion
Our results suggest that natural variation in FRZB is not a major contributor to the observed variability in peak BMD in either Chinese females or males. Because ethnic differences in the FRZB genotypes may exist, other studies in different population are required to confirm such results.
Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity
Authors: Müller Timo D , Brönner Günter , Wandolski Melanie , Carrie Jophia , Nguyen Trang T , Greene Brandon H , Scherag André , Grallert Harald , Vogel Carla IG , Scherag Susann , Rief Winfried , Wichmann Hans-Erich , Illig Thomas , Schäfer Helmut , Hebebrand Johannes , Hinney Anke 
Published: January 2010

Abstract

Background
The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity.

Methods
We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity.

Results
The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05).

Conclusions
As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the FAAH variants analyzed here at least do not seem to play a major role in the etiology of obesity within our samples.
Genetic diversity among Plasmodium falciparum field isolates in Pakistan measured with PCR genotyping of the merozoite surface protein 1 and 2
Authors: Ghanchi Najia K , Mårtensson Andreas , Ursing Johan , Jafri Sana , Bereczky Sándor , Hussain Rabia , Beg Mohammad A 
Published: January 2010

Abstract

Background
The genetic diversity of Plasmodium falciparum has been extensively studied in various parts of the world. However, limited data are available from Pakistan. This study aimed to establish molecular characterization of P. falciparum field isolates in Pakistan measured with two highly polymorphic genetic markers, i.e. the merozoite surface protein 1 (msp-1)and 2 (msp-2).

Methods
Between October 2005 and October 2007, 244 blood samples from patients with symptomatic blood-slide confirmed P. falciparum mono-infections attending the Aga Khan University Hospital, Karachi, or its collection units located in Sindh and Baluchistan provinces, Pakistan were collected. The genetic diversity of P. falciparum was analysed by length polymorphism following gel electrophoresis of DNA products from nested polymerase chain reactions (PCR) targeting block 2 of msp-1 and block 3 of msp-2, including their respective allelic families KI, MAD 20, RO33, and FC27, 3D7/IC.

Results
A total of 238/244 (98%) patients had a positive PCR outcome in at least one genetic marker; the remaining six were excluded from analysis. A majority of patients had monoclonal infections. Only 56/231 (24%) and 51/236 (22%) carried multiple P. falciparum genotypes in msp-1 and msp-2, respectively. The estimated total number of genotypes was 25 msp-1 (12 KI; 8 MAD20; 5 RO33) and 33 msp-2 (14 FC27; 19 3D7/IC).

Conclusions
This is the first report on molecular characterization of P. falciparum field isolates in Pakistan with regards to multiplicity of infection. The genetic diversity and allelic distribution found in this study is similar to previous reports from India and Southeast Asian countries with low malaria endemicity.
Monoketone analogs of curcumin, a new class of Fanconi anemia pathway inhibitors
Authors: Landais Igor , Hiddingh Sanne , McCarroll Matthew , Yang Chao , Sun Aiming , Turker Mitchell S , Snyder James P , Hoatlin Maureen E 
Published: December 2009

Abstract

Background
The Fanconi anemia (FA) pathway is a multigene DNA damage response network implicated in the repair of DNA lesions that arise during replication or after exogenous DNA damage. The FA pathway displays synthetic lethal relationship with certain DNA repair genes such as ATM (Ataxia Telangectasia Mutated) that are frequently mutated in tumors. Thus, inhibition of FANCD2 monoubiquitylation (FANCD2-Ub), a key step in the FA pathway, might target tumor cells defective in ATM through synthetic lethal interaction. Curcumin was previously identified as a weak inhibitor of FANCD2-Ub. The aim of this study is to identify derivatives of curcumin with better activity and specificity.

Results
Using a replication-free assay in Xenopus extracts, we screened monoketone analogs of curcumin for inhibition of FANCD2-Ub and identified analog EF24 as a strong inhibitor. Mechanistic studies suggest that EF24 targets the FA pathway through inhibition of the NF-kB pathway kinase IKK. In HeLa cells, nanomolar concentrations of EF24 inhibited hydroxyurea (HU)-induced FANCD2-Ub and foci in a cell-cycle independent manner. Survival assays revealed that EF24 specifically sensitizes FA-competent cells to the DNA crosslinking agent mitomycin C (MMC). In addition, in contrast with curcumin, ATM-deficient cells are twofold more sensitive to EF24 than matched wild-type cells, consistent with a synthetic lethal effect between FA pathway inhibition and ATM deficiency. An independent screen identified 4H-TTD, a compound structurally related to EF24 that displays similar activity in egg extracts and in cells.

Conclusions
These results suggest that monoketone analogs of curcumin are potent inhibitors of the FA pathway and constitute a promising new class of targeted anticancer compounds.
Quantum dots improve peptide detection in MALDI MS in a size dependent manner
Authors: Bailes Julian , Vidal Loïc , Ivanov Dimitri A , Soloviev Mikhail 
Published: December 2009

AbstractLaser Desorption Ionization Mass Spectrometry employs matrix which is co-crystallised with the analyte to achieve "soft ionization" that is the formation of ions without fragmentation. A variety of matrix-free and matrix-assisted LDI techniques and matrices have been reported to date. LDI has been achieved using ultra fine metal powders (UFMPs), desorption ionisation on silicon (DIOS), sol-gel assisted laser desorption/ionization (SGALDI), as well as with common MALDI matrices such as 2,5-dihydroxy benzoic acid (DHB), 3,5-dimethoxy-4-hydroxycinnamic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA) to name a few. A variety of matrix additives have been shown to improve matrix assisted desorption, including silicon nanowires (SiNW), carbon nanotubes (CNT), metal nanoparticles and nanodots. To our knowledge no evidence exists for the application of highly fluorescent CdSe/ZnS quantum dots to enhance MALDI desorption of biological samples. Here we report that although CdSe/ZnS quantum dots on their own can not substitute matrix in MALDI-MS, their presence has a moderately positive effect on MALDI desorption, improves the signal-to-noise ratio, peak quality and increases the number of detected peptides and the overall sequence coverage.
Excitatory and inhibitory effects of prolactin release activated by nerve stimulation in rat anterior pituitary
Authors: Zhang Ping , Liu Ling , Xie Cong-Jun , Wang Kai-Hu , Gao Li-Zhi , Ju Gong 
Published: December 2009

Abstract

Background
A series of studies showed the presence of substantial amount of nerve fibers and their close relationship with the anterior pituitary gland cells. Our previous studies have suggested that aside from the classical theory of humoral regulation, the rat anterior pituitary has direct neural regulation on adrenocorticotropic hormone release. In rat anterior pituitary, typical synapses are found on every type of the hormone-secreting cells, many on lactotrophs. The present study was aimed at investigating the physiological significance of this synaptic relationship on prolactin release.

Methods
The anterior pituitary of rat was sliced and stimulated with electrical field in a self-designed perfusion chamber. The perfusate was continuously collected in aliquots and measured by radioimmunoassay for prolactin levels. After statistic analysis, differences of prolactin concentrations within and between groups were outlined.

Results
The results showed that stimulation at frequency of 2 Hz caused a quick enhancement of prolactin release, when stimulated at 10 Hz, prolactin release was found to be inhibited which came slower and lasted longer. The effect of nerve stimulation on prolactin release is diphasic and frequency dependent.

Conclusions
The present in vitro study offers the first physiological evidence that stimulation of nerve fibers can affect prolactin release in rat anterior pituitary. Low frequency stimulation enhances prolactin release and high frequency mainly inhibits it.
Estrogen and inflammation modulate estrogen receptor alpha expression in specific tissues of the temporomandibular joint
Authors: Puri Jyoti , Hutchins Bob , Bellinger Larry L , Kramer Phillip R 
Published: December 2009

AbstractBackgroundEstrogen is known to play role in temporomandibular joint (TMJ) disorders and estrogen effects can be mediated by estrogen receptor (ER) alpha present in the TMJ. Cells expressing the estrogen receptor ERalpha are present in the temporomandibular joint (TMJ) but changes in expression due to estrogen and inflammation have not been characterized. In this study, ERalpha protein content and the number of cells expressing ERalpha was measured in 17 beta-estradiol-treated rats after inflammation was induced in the TMJ.MethodsSixteen ovariectomized female rats were divided into two groups such that one group received 17 beta estradiol (E2) and the other was given vehicle (VEH). Groups were then subdivided further, one received injections of saline and the other received Complete Freund's adjuvant (CFA) within the superior joint space of the TMJ. Thus the four groups include no E2/saline, E2/saline, no E2/CFA and E2/CFA. After treatment, the rats were sacrificed, and the TMJ anterior, disc, retrodiscal and synovial tissues were analyzed by western blot and immunocytochemistry. Positive stained cells were counted using a Nikon epifluorescent microscope.ResultsThe western blot showed that ERalpha protein significantly decreased with inflammation. The number of ERalpha-positive cells in the TMJ was not affected by inflammation or 17 beta-estradiol with exception of the retrodiscal tissue. In the retrodiscal tissue 17 beta-estradiol significantly decreased the number of ERalpha-positive cells but only in a non-inflamed joint.ConclusionsIn conclusion, inflammation and 17 beta-estradiol can modulate ERalpha expression in the TMJ but the effects are tissue specific.
Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression
Authors: Trinh Alice T , Ball Bret G , Weber Erin , Gallaher Timothy K , Gluzman-Poltorak Zoya , Anderson French , Basile Lena A 
Published: December 2009

Abstract

Background
Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone.

Methods
A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection.

Results
Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements in T-cell specific gene expression were observed with the incorporation of additional cis-regulatory elements, such as a human polyadenylation signal and intron 7 from the human ADA gene.

Conclusion
These studies suggest that the combination of an authentically regulated ADA gene in a murine retroviral vector, together with additional locus-specific regulatory refinements, will yield a vector with a safer profile and greater efficacy in terms of high-level, therapeutic, regulated gene expression for the treatment of ADA-deficient severe combined immunodeficiency.
IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients
Authors: Rajski Michal , Zanetti-Dällenbach Rosanna , Vogel Brigitte , Herrmann Richard , Rochlitz Christoph , Buess Martin 
Published: January 2010

Abstract

Background
Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.

Methods
We used an ex vivo culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. In vitro data were correlated with in vivo findings by comparing the results with published expression datasets on human cancer biopsies.

Results
Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (P = 0.029 - Norway/Stanford and P = 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (P = 0.007 - Bhattacharjee and P = 0.008 - Garber dataset).

Conclusion
Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.
See the related commentary by Werner and Bruchim: http://www.biomedcentral.com/1741-7015/8/2
Particle length-dependent titanium dioxide nanomaterials toxicity and bioactivity
Authors: Hamilton Raymond F , Wu Nianqiang , Porter Dale , Buford Mary , Wolfarth Michael , Holian Andrij 
Published: December 2009

Abstract

Background
Titanium dioxide (TiO2) nanomaterials have considerable beneficial uses as photocatalysts and solar cells. It has been established for many years that pigment-grade TiO2 (200 nm sphere) is relatively inert when internalized into a biological model system (in vivo or in vitro). For this reason, TiO2 nanomaterials are considered an attractive alternative in applications where biological exposures will occur. Unfortunately, metal oxides on the nanoscale (one dimension < 100 nm) may or may not exhibit the same toxic potential as the original material. A further complicating issue is the effect of modifying or engineering of the nanomaterial to be structurally and geometrically different from the original material.

Results
TiO2 nanospheres, short (< 5 μm) and long (> 15 μm) nanobelts were synthesized, characterized and tested for biological activity using primary murine alveolar macrophages and in vivo in mice. This study demonstrates that alteration of anatase TiO2 nanomaterial into a fibre structure of greater than 15 μm creates a highly toxic particle and initiates an inflammatory response by alveolar macrophages. These fibre-shaped nanomaterials induced inflammasome activation and release of inflammatory cytokines through a cathepsin B-mediated mechanism. Consequently, long TiO2 nanobelts interact with lung macrophages in a manner very similar to asbestos or silica.

Conclusions
These observations suggest that any modification of a nanomaterial, resulting in a wire, fibre, belt or tube, be tested for pathogenic potential. As this study demonstrates, toxicity and pathogenic potential change dramatically as the shape of the material is altered into one that a phagocytic cell has difficulty processing, resulting in lysosomal disruption.
Microdialysis assessment of peripheral metabolism in critical limb ischemia after endovascular revascularization
Authors: Tozzi Matteo , Muscianisi Elisa , Piffaretti Gabriele , Castelli Patrizio 
Published: December 2009

Abstract

Background
Critical limb ischemia is a chronic pathologic condition defined by the lack of blood flow in peripheral circulation. Microdialysis is a well-known and sensitive method for the early detection of tissue ischemia. The aim of the present study was to use microdialysis in order to analyse cellular metabolism changes after peripheral endovascular revascularization.

Methods
Ten patients diagnosed with critical limb ischemia was enrolled. CMA 60 (CMA® - Solna, Sweden) catheter with a 20 kDa cut-off was placed subcutaneously on the anterior aspect of the foot of both limbs. Samples were collected starting 12-hours before surgery and throughout the following 72-hours, using a CMA 600 (CMA® - Solna, Sweden) microdialysis analyser.

Results
Technical revascularization was successful in all cases. The cannulation was well tolerated in all patients. The site of catheter insertion healed easily in few days without infective complications in any case. Two patients underwent major amputation. After revascularization, glucose showed a strong increase (mean, 5.86 ± 1.52 mMol/L, p = .008). No restoration of the circadian rhythm was noted in patients who underwent major amputation. Glycerol concentration curves were not deductibles in both the ischemic and the control limbs (mean, 148.43 ± 42.13 mMol/L vs 178.44 ± 75.93 mMol/L, p = .348). Within the first 24-hours after revascularization, lactate concentration raised strongly (6.58 ± 1.56 mMol/L, p = .002): thereafter, it immediately decreased to a concentration similar to the control level (1.71 ± 1.69 mMol/L). In both patients who underwent major amputation, lactate did not show the typical peak of the successful revascularization. The trend of the lactate/pyruvate ratio after a brief initial decrease of the ratio increased again in both the patients who finally underwent amputation.

Conclusions
Restoration of glucose and glycerol circadian rhythm, coupled with low lactate concentration and lactate/pyruvate ratio seemed to be linked to good surgical outcome.