bluuebunny/crossref_metadata_2025 huggingface dataset:
Why do corporate codes of conduct fail? Women workers and clothing supply chains in Vietnam
Authors: Hoang Dong , Jones Bryn
Published: April 2012

Despite criticisms of their derivation and implementation, corporate codes of conduct (CoCs) continue to dominate debates on Corporate Social Responsibility and the informal regulation of worker exploitation and abuse by ‘sweatshops’ supplying northern multinational corporations (MNCs). Through analytical interrogation of existing literature and empirical evidence from Vietnamese case studies, two propositions are made to clarify the poor performance of CoCs. It is argued, firstly, that the extent of the control of MNCs over their subcontracting suppliers is misconceived and over-estimated because supply chains function more like networks than the hierarchies assumed by ‘principal-agent’ preconceptions. Conceptualizing such relationships instead as networks of conflicting political and economic imperatives amongst various sets of actors generates a second proposition derived from our case studies. The factory workers, their subcontractor employers, intermediary vendors and even the MNCs seeking CoC commitments, have convergent interests in violating key aspects of the codes and deceiving their auditors. The analysis evaluates the residual value of CoCs in light of these constraints and the options for improving labour regulation, with particular reference to the plight of disadvantaged women workers.
Prevalence and predictors of metabolic syndrome among healthy Saudi Adults
Authors: Alzahrani Abdullah M , Karawagh Abdullah M , Alshahrani Fahad M , Naser Tariq A , Ahmed Almoutaz Alkhier , Alsharef Emad H
Published: April 2012

The prevalence of metabolic syndrome was determined as a cross-sectional study among 600 healthy Saudi adults (52% males and 58% aged 35–50 years) attending National Guard clinics using the definition proposed by National Cholesterol Education Program Adult Treatment Panel III. The prevalence of metabolic syndrome was 21%. Only one third of the participants had normal weight (body mass index = 18.5–24.9). Central obesity based on waist circumferences was noted in 21% of males and 22% of females. Low high-density lipoprotein-C showed the highest prevalence (29%) followed by high triglyceride (24%). About 14% of participants had impaired fasting blood glucose (≥ 110 mg/dl). Only 6% had high blood pressure (≥ 130/85 mmHg). More than three quarters (77.3%) of the respondents had > 1 component of metabolic syndrome. In conclusion, metabolic syndrome needs to be addressed as an important health problem in the Gulf region.
Erlotinib appears to produce prolonged remission of insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease
Authors: Brooks Marvin B.
Published: April 2012

Patients with metabolic syndrome are at higher risk for type 2 diabetes and for chronic kidney disease. Metformin is the oral medication of choice for the treatment of type 2 diabetes in the absence of chronic kidney disease. There is a need for another oral glucose lowering agent for use in metabolic syndrome with type 2 diabetes and chronic kidney disease. We submit the first report of erlotinib, a once-daily oral medication for the treatment of non-small-cell lung cancer associated with specific genetic mutations, appearing to eliminate the need for insulin in insulin-requiring type 2 diabetes associated with metabolic syndrome and chronic kidney disease. The mechanism by which erlotinib, a tyrosine kinase inhibitor of the epidermal growth factor receptor may improve glycaemic control is unknown. Potential possibilities are explored.
CSII from patient to politics; a national and local perspective
Authors: Wake Deborah J , Mackay Liz , Jaap Alan , Strachan Mark W J , McKnight John A
Published: April 2012

Continuous subcutaneous infusion of insulin (CSII), or insulin pump therapy, is increasingly recognised as an important treatment option for type 1 diabetes. In the UK, however, patient usage remains low, owing in part to the politics surrounding funding. In this article, current CSII use in Scotland is discussed and the evidence base and cost effectiveness of the therapy, with respect to biochemical parameters and quality of life reviewed. The guidance on CSII use from national organisations (Scottish Intercollegiate Guideline Network and the National Institute for Health and Clinical Excellence) is also presented. There is strong support for CSII among patients, and personal patient stories are included to highlight the potential impact of CSII on everyday life. Finally, we discuss our local strategy for recruiting and commencing pump therapy and the local and national challenges faced. As CSII use increases, it is important that all doctors, nurses and allied health professionals have an awareness of what it is and how it works. Patients need ongoing support to best manage their health and health professionals should ensure that the most appropriate and cost-effective therapies are being offered.
Deepening shadows: The eclipse of press rights in Kyrgyzstan
Authors: Freedman Eric
Published: April 2012

In March 2005, a relatively nonviolent uprising ousted an authoritarian president in the former Soviet republic of Kyrgyzstan. In the aftermath of the so-called Tulip Revolution, press rights advocates and journalists welcomed the promise of greatly enhanced freedoms. However, the new regime proved to be as authoritarian and corrupt as its predecessor and little liberalization of the press system was evident five years later. Physical assaults continued, including murders, as did harassment, libel suits, impediments to access to information, license denials and self-censorship. There was only slow movement toward privatizing of state-owned media. Independent and oppositional media also remained in financial peril due to the country’s weak economy and high poverty level. Thus, 20 years after independence and a half-decade after the Tulip Revolution, the Soviet propaganda model for a press system was dead in name, but many major attributes survived, with significant implications for the continuum of authoritarianism in other postcommunist nations. The degree to which the April 2010 coup and subsequent constitutional change to a parliamentary democracy will spur an expansion of press rights and sustain market-based independent media outlets remains speculative amid grave concerns about continuing anti-press events.
Engagement of ubiquitination and de-ubiquitination at rostral ventrolateral medulla in experimental brain death
Authors: Wu Carol HY , Chan Julie YH , Chou Jimmy Li-Jer , Chan Samuel HH , Chang Alice YW
Published: April 2012

Background

Whereas brain death is a vitally important clinical phenomenon, our contemporary understanding on its underlying cellular mechanisms remains elusive. This study evaluated whether the ubiquitin-proteasome system (UPS) in the rostral ventrolateral medulla (RVLM), a neural substrate that our laboratory identified previously to be intimately related to brain death, is engaged in this fatal process.

Methods

We performed proteomics, Western Blot, real-time PCR, ELISA and pharmacological experiments in conjunction with a clinically relevant experimental endotoxemia model of brain death based on intravenous administration of Escherichia coli lipopolysaccharide in adult male Sprague–Dawley rats.

Results

Proteomics, Western blot and enzyme activity analyses demonstrated that polyubiquitination was preserved and de-ubiquitination by ubiquitin C-terminal hydrolase isozyme-L1 (UCH-L1) was sustained, alongside increased monoubiquitin availability or proteasome activity in RVLM over the course of experimental endotoxemia. However, real-time PCR revealed no significant alteration in proteasome subunit alpha type-1, ubiquitin or UCH-L1 at mRNA level. Functionally, whereas microinjection into the bilateral RVLM of proteasome inhibitors (lactacystin or proteasome inhibitor II) potentiated survival, an inhibitor of ubiquitin-recycling (ubiquitin aldehyde) or an UCH-L1 inhibitor exacerbated mortality.

Conclusions

We proposed previously that the progression towards brain death entails a tug-of-war between pro-death and pro-life programs in RVLM. It is conceivable that ubiquitination or de-ubiquitination in RVLM participate in brain death by regulating the degradation of the proteins involved in those programs.
Endotracheal intubation with airtraq® versus storz® videolaryngoscope in children younger than two years - a randomized pilot-study
Authors: Sørensen Martin Kryspin , Holm-Knudsen Rolf
Published: April 2012

Background

New laryngoscopes have become available for use in small children. The aim of the study was to compare the Storz® videolaryngoscope (SVL) to the Airtraq® Optical laryngoscope (AOL) for tracheal intubation in children younger than two years of age who had a normal airway assessment. Our hypothesis was that the SVL would have a better success rate than the AOL.

Methods

Ten children aged 2 years or younger scheduled for elective cleft lip/palate surgery were included. The anesthesia was standardized and a Cormack-Lehane (CL)-score was obtained using a Macintosh laryngoscope. After randomization CL-score and endotracheal tube positioning in front of the glottis was performed with one device, followed by the same procedure and intubation with the other device. The video-feed was recorded along with real-time audio. The primary endpoint was the success rate, defined as intubation in first attempt. Secondary endpoints were the time from start of laryngoscopy to CL-score, tube positioning in front of the glottis, and intubation.

Results

Two intubation attempts were needed in two of five patients randomized to the SVL. The difference in time (SVL vs. AOL) to CL-score was 4.5 sec (p = 0.0449). The difference in time (SVL vs. AOL) to tube positioning was 11.6 sec (p = 0.0015). Time to intubation was 29.0 sec for SVL and 15.8 sec for AOL.

Conclusion

No difference in the success rate of endotracheal intubation could be established in this ten patient sample of children younger than two years with a normal airway assessment scheduled for elective cleft lip/palate surgery. However, the Airtraq® Optical videolaryngoscope showed a number of time related advantages over the Storz® videolaryngoscope. Because of the small sample size a larger trial is needed to confirm these findings. Both devices were considered safe in all intubations.

Trial registration

ClinicalTrials.gov; Identifier NCT01090726.
Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines
Authors: Zou Zhengyun , Xie Li , Wei Jia , Yu Lixia , Qian Xiaoping , Chen Junhao , Wang Tingting , Liu Baorui
Published: April 2012

Background

Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death.

Methods

MTT assay was used to determine IC50 values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.

Conclusions

Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.
Reconstruction of cytosolic fumaric acid biosynthetic pathways in Saccharomyces cerevisiae
Authors: Xu Guoqiang , Liu Liming , Chen Jian
Published: April 2012

Background

Fumaric acid is a commercially important component of foodstuffs, pharmaceuticals and industrial materials, yet the current methods of production are unsustainable and ecologically destructive.

Results

In this study, the fumarate biosynthetic pathway involving reductive reactions of the tricarboxylic acid cycle was exogenously introduced in S. cerevisiae by a series of simple genetic modifications. First, the Rhizopus oryzae genes for malate dehydrogenase (RoMDH) and fumarase (RoFUM1) were heterologously expressed. Then, expression of the endogenous pyruvate carboxylase (PYC2) was up-regulated. The resultant yeast strain, FMME-001 ↑PYC2 + ↑RoMDH, was capable of producing significantly higher yields of fumarate in the glucose medium (3.18 ± 0.15 g liter-1) than the control strain FMME-001 empty vector.

Conclusions

The results presented here provide a novel strategy for fumarate biosynthesis, which represents an important advancement in producing high yields of fumarate in a sustainable and ecologically-friendly manner.
Development stage-specific proteomic profiling uncovers small, lineage specific proteins most abundant in the Aspergillus Fumigatus conidial proteome
Authors: Suh Moo-Jin , Fedorova Natalie D , Cagas Steven E , Hastings Susan , Fleischmann Robert D , Peterson Scott N , Perlin David S , Nierman William C , Pieper Rembert , Momany Michelle
Published: April 2012

Background

The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process.

Results

To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae in which germ tube emergence has just begun, and pre-septation hyphae. To enrich for glycan-linked cell wall proteins we used an alkaline cell extraction method. Shotgun proteomic resulted in the identification of 375 unique gene products with high confidence, with no evidence for enrichment of cell wall-immobilized and secreted proteins. The most interesting discovery was the identification of 52 proteins enriched in dormant conidia including 28 proteins that have never been detected in the A. fumigatus conidial proteome such as signaling protein Pil1, chaperones BipA and calnexin, and transcription factor HapB. Additionally we found many small, Aspergillus specific proteins of unknown function including 17 hypothetical proteins. Thus, the most abundant protein, Grg1 (AFUA_5G14210), was also one of the smallest proteins detected in this study (M.W. 7,367). Among previously characterized proteins were melanin pigment and pseurotin A biosynthesis enzymes, histones H3 and H4.1, and other proteins involved in conidiation and response to oxidative or hypoxic stress. In contrast, expanding conidia, hyphae with early germ tubes, and pre-septation hyphae samples were enriched for proteins responsible for housekeeping functions, particularly translation, respiratory metabolism, amino acid and carbohydrate biosynthesis, and the tricarboxylic acid cycle.

Conclusions

The observed temporal expression patterns suggest that the A. fumigatus conidia are dominated by small, lineage-specific proteins. Some of them may play key roles in host-pathogen interactions, signal transduction during conidial germination, or survival in hostile environments.
BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway
Authors: Kopf Jessica , Petersen Ansgar , Duda Georg N , Knaus Petra
Published: April 2012

Background

Efficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs) are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear.

Results

Here, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways.

Conclusions

Mechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.
Emerging complexities of APOBEC3G action on immunity and viral fitness during HIV infection and treatment
Authors: Monajemi Mahdis , Woodworth Claire F , Benkaroun Jessica , Grant Michael , Larijani Mani
Published: April 2012

The enzyme APOBEC3G (A3G) mutates the human immunodeficiency virus (HIV) genome by converting deoxycytidine (dC) to deoxyuridine (dU) on minus strand viral DNA during reverse transcription. A3G restricts viral propagation by degrading or incapacitating the coding ability of the HIV genome. Thus, this enzyme has been perceived as an innate immune barrier to viral replication whilst adaptive immunity responses escalate to effective levels. The discovery of A3G less than a decade ago led to the promise of new anti-viral therapies based on manipulation of its cellular expression and/or activity. The rationale for therapeutic approaches has been solidified by demonstration of the effectiveness of A3G in diminishing viral replication in cell culture systems of HIV infection, reports of its mutational footprint in virions from patients, and recognition of its unusually robust enzymatic potential in biochemical studies in vitro. Despite its effectiveness in various experimental systems, numerous recent studies have shown that the ability of A3G to combat HIV in the physiological setting is severely limited. In fact, it has become apparent that its mutational activity may actually enhance viral fitness by accelerating HIV evolution towards the evasion of both anti-viral drugs and the immune system. This body of work suggests that the role of A3G in HIV infection is more complex than heretofore appreciated and supports the hypothesis that HIV has evolved to exploit the action of this host factor. Here we present an overview of recent data that bring to light historical overestimation of A3G’s standing as a strictly anti-viral agent. We discuss the limitations of experimental systems used to assess its activities as well as caveats in data interpretation.
Human endometrial cell coculture reduces the endocrine disruptor toxicity on mouse embryo development
Authors: Lee Myeong-Seop , Lee Young-Sang , Lee Hae-Hyeog , Song Ho-Yeon
Published: April 2012

Backgrounds

Previous studies suggested that endocrine disruptors (ED) are toxic on preimplantation embryos and inhibit development of embryos in vitro culture. However, information about the toxicity of endocrine disruptors on preimplantation development of embryo in human reproductive environment is lacking.

Methods

Bisphenol A (BPA) and Aroclor 1254 (polychlorinated biphenyls) were used as endocrine disruptors in this study. Mouse 2-cell embryos were cultured in medium alone or vehicle or co-cultured with human endometrial epithelial layers in increasing ED concentrations.

Results

At 72 hours the percentage of normal blastocyst were decreased by ED in a dose-dependent manner while the co-culture system significantly enhanced the rate and reduced the toxicity of endocrine disruptors on the embryonic development in vitro.

Conclusions

In conclusion, although EDs have the toxic effect on embryo development, the co-culture with human endometrial cell reduced the preimplantation embryo from it thereby making human reproductive environment protective to preimplantation embryo from the toxicity of endocrine disruptors.
Kaempferol as a flavonoid induces osteoblastic differentiation via estrogen receptor signaling
Authors: Guo Ava Jiangyang , Choi Roy Chiyan , Zheng Ken Yuzhong , Chen Vicky Ping , Dong Tina Tingxia , Wang Zheng-Tao , Vollmer Günter , Lau David Taiwai , Tsim Karl Wah-keung
Published: April 2012

Background

Flavonoids, a group of compounds mainly derived from vegetables and herbal medicines, chemically resemble estrogen and some have been used as estrogen substitutes. Kaempferol, a flavonol derived from the rhizome of Kaempferia galanga L., is a well-known phytoestrogen possessing osteogenic effects that is also found in a large number of plant foods.

The herb K. galanga is a popular traditional aromatic medicinal plant that is widely used as food spice and in medicinal industries. In the present study, both the estrogenic and osteogenic properties of kaempferol are evaluated.

Methods

Kaempferol was first evaluated for its estrogenic properties, including its effects on estrogen receptors. The osteogenic properties of kaempferol were further determined its induction effects on specific osteogenic enzymes and genes as well as the mineralization process in cultured rat osteoblasts.

Results

Kaempferol activated the transcriptional activity of pERE-Luc (3.98 ± 0.31 folds at 50 μM) and induced estrogen receptor α (ERα) phosphorylation in cultured rat osteoblasts, and this ER activation was correlated with induction and associated with osteoblast differentiation biomarkers, including alkaline phosphatase activity and transcription of osteoblastic genes, e.g., type I collagen, osteonectin, osteocalcin, Runx2 and osterix. Kaempferol also promoted the mineralization process of osteoblasts (4.02 ± 0.41 folds at 50 μM). ER mediation of the kaempferol-induced effects was confirmed by pretreatment of the osteoblasts with an ER antagonist, ICI 182,780, which fully blocked the induction effect.

Conclusion

Our results showed that kaempferol stimulates osteogenic differentiation of cultured osteoblasts by acting through the estrogen receptor signaling.
The choice of the intravenous fluid influences the tolerance of acute normovolemic anemia in anesthetized domestic pigs
Authors: Pape Andreas , Kutschker Saskia , Kertscho Harry , Stein Peter , Horn Oliver , Lossen Mischa , Zwissler Bernhard , Habler Oliver
Published: April 2012

Introduction

The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O2) supply during acute normovolemic anemia has not been investigated so far.

Methods

Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O2-consumption (VO2). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O2 transport and tissue oxygenation.

Results

In each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO2), and O2 extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit.

Conclusions

The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function.
A metagenomic study of diet-dependent interaction between gut microbiota and host in infants reveals differences in immune response
Authors: Schwartz Scott , Friedberg Iddo , Ivanov Ivan V , Davidson Laurie A , Goldsby Jennifer S , Dahl David B , Herman Damir , Wang Mei , Donovan Sharon M , Chapkin Robert S
Published: April 2012

Background

Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly affecting the health and well-being of the host. Thus, it is important to develop a synthetic approach to study the host transcriptome and the microbiome simultaneously. Early microbial colonization in infants is critically important for directing neonatal intestinal and immune development, and is especially attractive for studying the development of human-commensal interactions. Here we report the results from a simultaneous study of the gut microbiome and host epithelial transcriptome of three-month-old exclusively breast- and formula-fed infants.

Results

Variation in both host mRNA expression and the microbiome phylogenetic and functional profiles was observed between breast- and formula-fed infants. To examine the interdependent relationship between host epithelial cell gene expression and bacterial metagenomic-based profiles, the host transcriptome and functionally profiled microbiome data were subjected to novel multivariate statistical analyses. Gut microbiota metagenome virulence characteristics concurrently varied with immunity-related gene expression in epithelial cells between the formula-fed and the breast-fed infants.

Conclusions

Our data provide insight into the integrated responses of the host transcriptome and microbiome to dietary substrates in the early neonatal period. We demonstrate that differences in diet can affect, via gut colonization, host expression of genes associated with the innate immune system. Furthermore, the methodology presented in this study can be adapted to assess other host-commensal and host-pathogen interactions using genomic and transcriptomic data, providing a synthetic genomics-based picture of host-commensal relationships.
Concentration of endogenous estrogens and estrogen metabolites in the NCI-60 human tumor cell lines
Authors: Xu Xia , Veenstra Timothy D
Published: April 2012

Background

Endogenous estrogens and estrogen metabolites play an important role in the pathogenesis and development of human breast, endometrial, and ovarian cancers. Increasing evidence also supports their involvement in the development of certain lung, colon and prostate cancers.

Methods

In this study we systemically surveyed endogenous estrogen and estrogen metabolite levels in each of the NCI-60 human tumor cell lines, which include human breast, central nerve system, colon, ovarian, prostate, kidney and non-small cell lung cancers, as well as melanomas and leukemia. The absolute abundances of these metabolites were measured using a liquid chromatography-tandem mass spectrometry method that has been previously utilized for biological fluids such as serum and urine.

Results

Endogenous estrogens and estrogen metabolites were found in all NCI-60 human tumor cell lines and some were substantially elevated and exceeded the levels found in well known estrogen-dependent and estrogen receptor-positive tumor cells such as MCF-7 and T-47D. While estrogens were expected to be present at high levels in cell lines representing the female reproductive system (that is, breast and ovarian), other cell lines, such as leukemia and colon, also contained very high levels of these steroid hormones. The leukemia cell line RMPI-8226 contained the highest levels of estrone (182.06 pg/106 cells) and 17β-estradiol (753.45 pg/106 cells). In comparison, the ovarian cancer cell line with the highest levels of these estrogens contained only 19.79 and 139.32 pg/106 cells of estrone and 17β-estradiol, respectively. The highest levels of estrone and 17β-estradiol in breast cancer cell lines were only 8.45 and 87.37 pg/106 cells in BT-549 and T-47D cells, respectively.

Conclusions

The data provided evidence for the presence of significant amounts of endogenous estrogens and estrogen metabolites in cell lines not commonly associated with these steroid hormones. This broad discovery of endogenous estrogens and estrogen metabolites in these cell lines suggest that several human tumors may be beneficially treated using endocrine therapy aimed at estrogen biosynthesis and estrogen-related signaling pathways.
Cancer detection and biopsy classification using concurrent histopathological and metabolomic analysis of core biopsies
Authors: Brown Meredith V , McDunn Jonathan E , Gunst Philip R , Smith Elizabeth M , Milburn Michael V , Troyer Dean A , Lawton Kay A
Published: April 2012

Background

Metabolomics, the non-targeted interrogation of small molecules in a biological sample, is an ideal technology for identifying diagnostic biomarkers. Current tissue extraction protocols involve sample destruction, precluding additional uses of the tissue. This is particularly problematic for high value samples with limited availability, such as clinical tumor biopsies that require structural preservation to histologically diagnose and gauge cancer aggressiveness. To overcome this limitation and increase the amount of information obtained from patient biopsies, we developed and characterized a workflow to perform metabolomic analysis and histological evaluation on the same biopsy sample.

Methods

Biopsies of ten human tissues (muscle, adrenal gland, colon, lung, pancreas, small intestine, spleen, stomach, prostate, kidney) were placed directly in a methanol solution to recover metabolites, precipitate proteins, and fix tissue. Following incubation, biopsies were removed from the solution and processed for histology. Kidney and prostate cancer tumor and benign biopsies were stained with hemotoxylin and eosin and prostate biopsies were subjected to PIN-4 immunohistochemistry. The methanolic extracts were analyzed for metabolites on GC/MS and LC/MS platforms. Raw mass spectrometry data files were automatically extracted using an informatics system that includes peak identification and metabolite identification software.

Results

Metabolites across all major biochemical classes (amino acids, peptides, carbohydrates, lipids, nucleotides, cofactors, xenobiotics) were measured. The number (ranging from 260 in prostate to 340 in colon) and identity of metabolites were comparable to results obtained with the current method requiring 30 mg ground tissue. Comparing relative levels of metabolites, cancer tumor from benign kidney and prostate biopsies could be distinguished. Successful histopathological analysis of biopsies by chemical staining (hematoxylin, eosin) and antibody binding (PIN-4, in prostate) showed cellular architecture and immunoreactivity were retained.

Conclusions

Concurrent metabolite extraction and histological analysis of intact biopsies is amenable to the clinical workflow. Methanol fixation effectively preserves a wide range of tissues and is compatible with chemical staining and immunohistochemistry. The method offers an opportunity to augment histopathological diagnosis and tumor classification with quantitative measures of biochemicals in the same tissue sample. Since certain biochemicals have been shown to correlate with disease aggressiveness, this method should prove valuable as an adjunct to differentiate cancer aggressiveness.
Multi-platform characterization of the human cerebrospinal fluid metabolome: a comprehensive and quantitative update
Authors: Mandal Rupasri , Guo An Chi , Chaudhary Kruti K , Liu Philip , Yallou Faizath S , Dong Edison , Aziat Farid , Wishart David S
Published: April 2012

Background

Human cerebral spinal fluid (CSF) is known to be a rich source of small molecule biomarkers for neurological and neurodegenerative diseases. In 2007, we conducted a comprehensive metabolomic study and performed a detailed literature review on metabolites that could be detected (via metabolomics or other techniques) in CSF. A total of 308 detectable metabolites were identified, of which only 23% were shown to be routinely identifiable or quantifiable with the metabolomics technologies available at that time. The continuing advancement in analytical technologies along with the growing interest in CSF metabolomics has led us to re-visit the human CSF metabolome and to re-assess both its size and the level of coverage than can be achieved with today's technologies.

Methods

We used five analytical platforms, including nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), direct flow injection-mass spectrometry (DFI-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS) to perform quantitative metabolomics on multiple human CSF samples. This experimental work was complemented with an extensive literature review to acquire additional information on reported CSF compounds, their concentrations and their disease associations.

Results

NMR, GC-MS and LC-MS methods allowed the identification and quantification of 70 CSF metabolites (as previously reported). DFI-MS/MS allowed the quantification of 78 metabolites (6 acylcarnitines, 13 amino acids, hexose, 42 phosphatidylcholines, 2 lyso-phosphatidylcholines and 14 sphingolipids), while ICP-MS provided quantitative results for 33 metal ions in CSF. Literature analysis led to the identification of 57 more metabolites. In total, 476 compounds have now been confirmed to exist in human CSF.

Conclusions

The use of improved metabolomic and other analytical techniques has led to a 54% increase in the known size of the human CSF metabolome over the past 5 years. Commonly available metabolomic methods, when combined, can now routinely identify and quantify 36% of the 'detectable' human CSF metabolome. Our experimental works measured 78 new metabolites that, as per our knowledge, have not been reported to be present in human CSF. An updated CSF metabolome database containing the complete set of 476 human CSF compounds, their concentrations, related literature references and links to their known disease associations is freely available at the CSF metabolome database.
Editorial: Acute pancreatitis and neutrophil gelatinase MMP9: don't get me started!
Authors: Tracy Thomas F
Published: April 2012

Discussion on the mechanisms of injury that follow acute pancreatitis.
Editorial: HDAC inhibition begets more MDSCs
Authors: Reddy Pavan
Published: April 2012

Discussion on HDAC inhibition-mediated immune-regulation and generating MDSCs with greater efficiency, both in vitro and in vivo.
Quantitative log interpretation and uncertainty propagation of petrophysical properties and facies classification from rock-physics modeling and formation evaluation analysis
Authors: Grana Dario , Pirrone Marco , Mukerji Tapan
Published: April 2012

Formation evaluation analysis, rock-physics models, and log-facies classification are powerful tools to link the physical properties measured at wells with petrophysical, elastic, and seismic properties. However, this link can be affected by several sources of uncertainty. We proposed a complete statistical workflow for obtaining petrophysical properties at the well location and the corresponding log-facies classification. This methodology is based on traditional formation evaluation models and cluster analysis techniques, but it introduces a full Monte Carlo approach to account for uncertainty evaluation. The workflow includes rock-physics models in log-facies classification to preserve the link between petrophysical properties, elastic properties, and facies. The use of rock-physics model predictions guarantees obtaining a consistent set of well-log data that can be used both to calibrate the usual physical models used in seismic reservoir characterization and to condition reservoir models. The final output is the set of petrophysical curves with the associated uncertainty, the profile of the facies probabilities, and the entropy, or degree of confusion, related to the most probable facies profile. The full statistical approach allows us to propagate the uncertainty from data measured at the well location to the estimated petrophysical curves and facies profiles. We applied the proposed methodology to two different well-log studies to determine its applicability, the advantages of the new integrated approach, and the value of uncertainty analysis.
Whistleblowing, organisational harm and the self-regulating organisation
Authors: Pemberton Simon , Tombs Steve , Chan Ming Ming Joiy , Seal Lizzie
Published: April 2012

Whistleblowing has emerged as a key element of regulatory strategy. This article provides a brief, theoretical analysis of the claimed affinities between whistleblowing, self-regulation and corporate social responsibility. It then addresses a series of key issues in relation to whistleblowing: the individual, organisational and social characteristics associated with the decision to blow the whistle (or not); the consequences of reporting organisational harm for whistleblowers; and the robustness of legal protections for those who report such harm. Finally, it raises a series of challenges to the idea, reality and potential of whistleblowing as part of an effective self-regulatory strategy.
Policy transfer and convergence within the UK: the case of local government performance improvement regimes
Authors: Nutley Sandra , Downe James , Martin Steve , Grace Clive
Published: April 2012

Analysis of the development and implementation of local government performance improvement regimes in England, Scotland and Wales over the last decade reveals congruence in policy goals but divergence in policy implementation and outcomes. The governments in all three countries had a common aim of improving local government performance. However, differences in ideology, the nature of central–local government relations, the numbers of councils and a political imperative for newly devolved administrations to be seen to pursue ‘home-grown’ solutions limited policy learning between different parts of the United Kingdom (UK) and in the case of Wales fuelled determined policy avoidance by policy makers.
Recent trends in ice cover duration for Lake Morskie Oko (Tatra Mountains, East-Central Europe)
Authors: Pociask-Karteczka Joanna , Choiński Adam
Published: April 2012

The study examined the formation, break-up, and duration of ice phenomena and ice cover on Lake Morskie Oko (1,395.4 metres above sea level (masl)), which is a representative of high mountain lakes in the Tatra Mountains located in the western Carpathian Mountains with a maximum elevation of 2,655 masl in the period 1971–2010. The maximum thickness was analyzed additionally. The lake covers an area of nearly 32 hectares and its greatest depth is 51.8 m. Its water is very clear with transparency reaching 12.5 m in depth. The trend towards a delayed freeze-up reaches 4.1 days per decade (d decade−1) (p < 0.01) and the ablation of ice on Lake Morskie Oko tends to take place earlier at a rate of 4.5 d decade−1 (p < 0.05). The time period with ice cover on the lake has been getting shorter at a rate of 10 d decade−1 during the time frame of interest. Results of ice cover research on Lake Morskie Oko are consistent with recent studies which have shown that ice duration on lakes throughout the Northern Hemisphere has decreased over the last few decades and they serve as new evidence which confirms a warming of the climate in this section of Europe.
Hydraulic performance of small free water surface constructed wetlands treating sugar factory effluent in western Kenya
Authors: Bodin Hristina , Persson Jesper
Published: April 2012

This study investigated, using a lithium salt tracer, how macrophyte species and hydraulic loading rate (HLR) of wastewater influenced hydraulics in constructed wetlands (CWs). Four pilot-scale CWs received 45 mm day−1 of pre-treated sugar factory effluent and another four received 110 mm day−1. Half the CWs were planted with Cyperus papyrus and half with Echinochloa pyramidalis. Results showed a significant negative connection between tracer mass recovery and wetland water leakages. Also, a significant negative relationship between active wetland water volume and macrophyte density was detected. Further, a significant effect of HLR on mass removal rates of NH4+-N was observed. However, no significant effect of either HLR or macrophyte species on wetland hydraulic parameters was found.
Multi-objective optimization of the management of a waterworks using an integrated well field model
Authors: Hansen Annette K. , Madsen Henrik , Bauer-Gottwein Peter , Falk Anne Katrine V. , Rosbjerg Dan
Published: April 2012

This study uses multi-objective optimization of an integrated well field model to improve the management of a waterworks. The well field model, called WELLNES (WELL field Numerical Engine Shell) is a dynamic coupling of a groundwater model, a pipe network model, and a well model. WELLNES is capable of predicting the water level and the energy consumption of the individual production wells. The model has been applied to Søndersø waterworks in Denmark, where it predicts the energy consumption within 1.8% of the observed. The objectives of the optimization problem are to minimize the specific energy of the waterworks and to avoid inflow of contaminated water from a nearby contaminated site. The decision variables are the pump status (on/off), and the constraint is that the waterworks has to provide a certain amount of drinking water. The advantage of multi-objective optimization is that the Pareto curve provides the decision-makers with compromise solutions between the two competing objectives. In the test case the Pareto optimal solutions are compared with an exhaustive benchmark solution. It is shown that the energy consumption can be reduced by 4% by changing the pumping configuration without violating the protection against contamination.
Accumulation of heavy metals in Medicago sativa L. and Trifolium pratense L. at the contaminated fluvisol
Authors: Jaksic Snezana , Vuckovic Savo , Vasiljevic Sanja , Grahovac Nada , Popovic Vera , Sunjka Dragana , Dozet Gordana
Published: April 2012

Recently, heavy metals concentrations increased in some agricultural areas
due to the consequences of anthropogenic impacts. The aim of this study was
to determine the level of heavy metals (As, Cr, Ni and Pb) in Medicago sativa
L. and Trifolium pratense L. grown on fluvisol, in order to obtain
information on safety of these nutrients. The total content of Pb, As, Cr and
Ni in the samples of fluvisol was above the maximum allowable amount. The
content of heavy metals in Medicago sativa L. and Trifolium pratense L. was
below the critical and toxic concentrations in all samples originating from
contaminated soil. It was concluded that the accumulation of heavy metals in
plants did not depend only on the total content in soil, but also the
affinity of the plant, and individual and interactive effects of various soil
properties. No statistically significant differences in the accumulation of
heavy metals between Medicago sativa L. and Trifolium pratense L were
observed. It is necessary to further control of heavy metals in the
investigated area, in order to prevent their entry into the food chain and
provide healthy food.
The development of simple calculation model for energy performance of double skin façades
Authors: Andjelkovic Aleksandar , Cvjetkovic Tanja , Djakovic Damir , Stojanovic Ivan
Published: April 2012

Estimating thermal effect of so called double-skin fa?ades on energy
performance of buildings with two envelopes, a proprietary mathematical model
of heat transfer through double-skin fa?ades has been developed. A very
specific approach of the mathematical model presented here is based on
prediction of the double-skin fa?ades interspace temperature and assumption
that fa?ade could be treated as a single one declaring the interspace
temperature and reduced intensity of solar radiation as the ?outdoor?
conditions. In this paper results of the heating and cooling loads as well as
the interspace temperature prediction compared for three months (January,
April and July) and for the west oriented fa?ade with ordinary and absorption
glass are presented. Fa?ade is placed under climatic conditions of Belgrade
(45? North Latitude). Also, results for weather conditions of sunny and
cloudy day are shown. Results includes influence of air velocity in
interspace of fa?ades for April and July. Following a type of the double-skin
fa?ade construction assumption it was implied that the space between the two
envelopes is closed during the winter mode for air circulation, in order to
have temperature higher inside than outside and opposite in the summer mode,
air inlet and outlet are opened in order to prevent much higher temperatures
than the outside ones, and higher cooling load of an air-conditioned
building, as a consequence. Taking only thermal effects into account,
presented prediction has proven that double-skin fa?ades decrease both
building heat losses and heat gains throughout the year, and give significant
contribution to the building energy consumption savings.
About the Serbian energy efficiency problems
Authors: Gvozdenac Dusan , Simic Tihomir
Published: April 2012

This paper analyzes energy efficiency in Serbia. The analysis has been done
on the basis of energy intensity indicators for Serbia and neighboring
countries, and some other countries and regions. It relates to the period of
some ten years and it is directed to the consideration of required
interventions regarding the change of the National Energy Efficiency Policy.
Regardless of constant attempts to improve and increase energy efficiency and
to expand utilization of renewable energy sources, it seems that accomplished
results are still very modest. The analysis of several energy indicators and
their changes in the midterm period confirms this statement.