bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein-lipid interactions: correlation of a predictive algorithm for lipid-binding sites with three-dimensional structural data
Authors: Scott David L , Diez Gerold , Goldmann Wolfgang H 
Published: April 2006

Abstract

Background
Over the past decade our laboratory has focused on understanding how soluble cytoskeleton-associated proteins interact with membranes and other lipid aggregates. Many protein domains mediating specific cell membrane interactions appear by fluorescence microscopy and other precision techniques to be partially inserted into the lipid bilayer. It is unclear whether these protein-lipid-interactions are dependent on shared protein motifs or unique regional physiochemistry, or are due to more global characteristics of the protein.

Results
We have developed a novel computational program that predicts a protein's lipid-binding site(s) from primary sequence data. Hydrophobic labeling, Fourier transform infrared spectroscopy (FTIR), film balance, T-jump, CD spectroscopy and calorimetry experiments confirm that the interfaces predicted for several key cytoskeletal proteins (alpha-actinin, Arp2, CapZ, talin and vinculin) partially insert into lipid aggregates. The validity of these predictions is supported by an analysis of the available three-dimensional structural data. The lipid interfaces predicted by our algorithm generally contain energetically favorable secondary structures (e.g., an amphipathic alpha-helix flanked by a flexible hinge or loop region), are solvent-exposed in the intact protein, and possess favorable local or global electrostatic properties.

Conclusion
At present, there are few reliable methods to determine the region of a protein that mediates biologically important interactions with lipids or lipid aggregates. Our matrix-based algorithm predicts lipid interaction sites that are consistent with the available biochemical and structural data. To determine whether these sites are indeed correctly identified, and whether use of the algorithm can be safely extended to other classes of proteins, will require further mapping of these sites, including genetic manipulation and/or targeted crystallography.
Cardiovascular system in larval zebrafish responds to developmental hypoxia in a family specific manner
Authors: Moore Francisco B-G , Hosey Michelle , Bagatto Brian 
Published: April 2006

AbstractBackgroundGenetic and environmental variation are both known to influence development. Evolution of a developmental response that is optimized to the environment (adaptive plasticity) requires the existence of genetic variation for that developmental response. In complex traits composed of integrated sets of subsidiary traits, the adaptive process may be slowed by the existence of multiple possible integrated responses. This study tests for family (sibship) specific differences in plastic response to hypoxia in an integrated set of cardiovascular traits in zebrafish.ResultsCardiac output, which is the integrated product of several subsidiary traits, varied highly significantly between families, and families differed significantly in the degree and direction of response to developmental oxygen level. The cardiac output response to oxygen environment was entirely family specific with no significant overall trend due to oxygen level. Constituent physiological variables that contribute to cardiac output all showed significant family specific response to hypoxia. Traits that were not directly related to cardiac output, such as arterial and venous diameter, and red blood cell velocities did not respond to hypoxia in a family specific manner.ConclusionZebrafish families vary in their plastic response to hypoxia. Genetic variation in plastic response to hypoxia may therefore provide the basic ingredient for adaptation to a variable environment. Considerable variation in the degree of familial response to hypoxia exists between different cardiovascular traits that may contribute to cardiac output. It is possible that the integration of several subsidiary traits into cardiac output allows the maintenance of genetic variance in cardiac response.
Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle
Authors: Klinger Francesca G , Battista Natalia , De Felici Massimo , Maccarrone Mauro 
Published: April 2006

Abstract
Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues.
Localization of deformed wing virus infection in queen and drone Apis mellifera L
Authors: Fievet Julie , Tentcheva Diana , Gauthier Laurent , de Miranda Joachim , Cousserans François , Colin Marc Edouard , Bergoin Max 
Published: April 2006

Abstract
The distribution of deformed wing virus infection within the honey bee reproductive castes (queens, drones) was investigated by in situ hybridization and immunohistology from paraffin embedded sections. Digoxygenin or CY5.5 fluorochrome end-labelled nucleotide probes hybridizing to the 3' portion of the DWV genome were used to identify DWV RNA, while a monospecific antibody to the DWV-VP1 structural protein was used to identify viral proteins and particles. The histological data were confirmed by quantitative RT-PCR of dissected organs. Results showed that DWV infection is not restricted to the digestive tract of the bee but spread in the whole body, including queen ovaries, queen fat body and drone seminal vesicles.
Evaluation of three Polymerase chain reaction tests targeting morphological transforming region II, UL-83 gene and glycoprotein O gene for the detection of Human Cytomegalovirus genome in clinical specimens of immunocompromised patients in Chennai, India
Authors: Sowmya P , Madhavan HN , Therese KL 
Published: April 2006

Abstract

Background
Human Cytomegalovirus (HCMV) continues to be an important cause of morbidity and occasional mortality in immunocompromised patients. Polymerase chain reaction (PCR) is the most sensitive and commonly used method for the assessment of HCMV infection in the immunocompromised patients at risk from severe associated clinical manifestations. However, there is little consistency in the qualitative PCR used for different regions of HCMV genome. Therefore, the performance of three Qualitative PCR tests to detect HCMV genome in clinical specimens from immunocompromised patients was evaluated. With pp65 antigenemia assay as the "gold standard", nested PCR for morphological transforming region II (mtr II) and glycoprotein O (gO) gene and uniplex PCR for UL 83 gene were applied on 92 consecutive clinical specimens obtained from 74 immunocompromised patients with clinically suspected HCMV disease. Virus isolation was attempted on 12 clinical specimens from six pp65 antigenemia positive patients. Based on the pp 65 antigenemia results as "gold standard", the sensitivity, specificity, positive predictive value and negative predictive value for each PCR was calculated.

Results
The PCR targeting mtr II region showed a higher sensitivity (100%) and negative predictive value (100%) than the other two PCRs in detecting HCMV DNA from clinical specimens obtained from different immunocompromised patient population of Chennai region, India.

Conclusion
The results suggests that the optimal method of detection of HCMV DNA could be achieved by PCR using primer sequences targeting mtr II region of genome of HCMV in Chennai region, India.
Toward a treaty on safety and cost-effectiveness of pharmaceuticals and medical devices: enhancing an endangered global public good
Authors: Faunce Thomas Alured 
Published: April 2006

Abstract
• Expert evaluations of the safety, efficacy and cost-effectiveness of pharmaceutical and medical devices, prior to marketing approval or reimbursement listing, collectively represent a globally important public good. The scientific processes involved play a major role in protecting the public from product risks such as unintended or adverse events, sub-standard production and unnecessary burdens on individual and governmental healthcare budgets.
• Most States now have an increasing policy interest in this area, though institutional arrangements, particularly in the area of cost-effectiveness analysis of medical devices, are not uniformly advanced and are fragile in the face of opposing multinational industry pressure to recoup investment and maintain profit margins.
• This paper examines the possibility, in this context, of States commencing negotiations toward bilateral trade agreement provisions, and ultimately perhaps a multilateral Treaty, on safety, efficacy and cost-effectiveness analysis of pharmaceuticals and medical devices. Such obligations may robustly facilitate a conceptually interlinked, but endangered, global public good, without compromising the capacity of intellectual property laws to facilitate local product innovations.
Tacit knowledge as the unifying factor in evidence based medicine and clinical judgement
Authors: Thornton Tim 
Published: April 2006

Abstract
The paper outlines the role that tacit knowledge plays in what might seem to be an area of knowledge that can be made fully explicit or codified and which forms a central element of Evidence Based Medicine. Appeal to the role the role of tacit knowledge in science provides a way to unify the tripartite definition of Evidence Based Medicine given by Sackett et al: the integration of best research evidence with clinical expertise and patient values. Each of these three elements, crucially including research evidence, rests on an ineliminable and irreducible notion of uncodified good judgement.
The paper focuses on research evidence, drawing first on the work of Kuhn to suggest that tacit knowledge contributes, as a matter of fact, to puzzle solving within what he calls normal science. A stronger argument that it must play a role in research is first motivated by looking to Collins' first hand account of replication in applied physics and then broader considerations of replication in justifying knowledge claims in scientific research. Finally, consideration of an argument from Wittgenstein shows that whatever explicit guidelines can be drawn up to guide judgement the specification of what counts as correctly following them has to remain implicit.
Overall, the paper sets out arguments for the claim that even though explicit guidelines and codifications can play a practical role in informing clinical practice, they rest on a body of tacit or implicit skill that is in principle ineliminable. It forms the bedrock of good judgement and unites the integration of research, expertise and values.
The membrane targeted apoptosis modulators erucylphosphocholine and erucylphosphohomocholine increase the radiation response of human glioblastoma cell lines in vitro
Authors: Rübel Amelie , Handrick René , Lindner Lars H , Steiger Matthias , Eibl Hansjörg , Budach Wilfried , Belka Claus , Jendrossek Verena 
Published: April 2006

Abstract

Background
Alkylphosphocholines constitute a novel class of antineoplastic synthetic phospholipid derivatives that induce apoptosis of human tumor cell lines by targeting cellular membranes. We could recently show that the first intravenously applicable alkylphosphocholine erucylphosphocholine (ErPC) is a potent inducer of apoptosis in highly resistant human astrocytoma/glioblastoma cell lines in vitro. ErPC was shown to cross the blood brain barrier upon repeated intravenous injections in rats and thus constitutes a promising candidate for glioblastoma therapy. Aim of the present study was to analyze putative beneficial effects of ErPC and its clinically more advanced derivative erucylphosphohomocholine (erucyl-N, N, N-trimethylpropanolaminphosphate, ErPC3, Erufosine™ on radiation-induced apoptosis and eradication of clonogenic tumor cells in human astrocytoma/glioblastoma cell lines in vitro.

Results
While all cell lines showed high intrinsic resistance against radiation-induced apoptosis as determined by fluorescence microscopy, treatment with ErPC and ErPC3 strongly increased sensitivity of the cells to radiation-induced cell death (apoptosis and necrosis). T98G cells were most responsive to the combined treatment revealing highly synergistic effects while A172 showed mostly additive to synergistic effects, and U87MG cells sub-additive, additive or synergistic effects, depending on the respective radiation-dose, drug-concentration and treatment time. Combined treatment enhanced therapy-induced damage of the mitochondria and caspase-activation. Importantly, combined treatment also increased radiation-induced eradication of clonogenic T98G cells as determined by standard colony formation assays.

Conclusion
Our observations make the combined treatment with ionizing radiation and the membrane targeted apoptosis modulators ErPC and ErPC3 a promising approach for the treatment of patients suffering from malignant glioma. The use of this innovative treatment concept in an in vivo xenograft setting is under current investigation.
Growth of a human mammary tumor cell line is blocked by galangin, a naturally occurring bioflavonoid, and is accompanied by down-regulation of cyclins D3, E, and A
Authors: Murray Tessa J , Yang Xinhai , Sherr David H 
Published: April 2006

Abstract
Introduction
This study was designed to determine if and how a non-toxic, naturally occurring bioflavonoid, galangin, affects proliferation of human mammary tumor cells. Our previous studies demonstrated that, in other cell types, galangin is a potent inhibitor of the aryl hydrocarbon receptor (AhR), an environmental carcinogen-responsive transcription factor implicated in mammary tumor initiation and growth control. Because some current breast cancer therapeutics are ineffective in estrogen receptor (ER) negative tumors and since the AhR may be involved in breast cancer proliferation, the effects of galangin on the proliferation of an ER-, AhRhigh line, Hs578T, were studied.

Methods
AhR expression and function in the presence or absence of galangin, a second AhR inhibitor, α-naphthoflavone (α-NF), an AhR agonist, indole-3-carbinol, and a transfected AhR repressor-encoding plasmid (FhAhRR) were studied in Hs578T cells by western blotting for nuclear (for instance, constitutively activated) AhR and by transfection of an AhR-driven reporter construct, pGudLuc. The effects of these agents on cell proliferation were studied by 3H-thymidine incorporation and by flow cytometry. The effects on cyclins implicated in mammary tumorigenesis were evaluated by western blotting.

Results
Hs578T cells were shown to express high levels of constitutively active AhR. Constitutive and environmental chemical-induced AhR activity was profoundly suppressed by galangin as was cell proliferation. However, the failure of α-NF or FhAhRR transfection to block proliferation indicated that galangin-mediated AhR inhibition was either insufficient or unrelated to its ability to significantly block cell proliferation at therapeutically relevant doses (IC50 = 11 μM). Galangin inhibited transition of cells from the G0/G1 to the S phases of cell growth, likely through the nearly total elimination of cyclin D3. Expression of cyclins A and E was also suppressed.

Conclusion
Galangin is a strong inhibitor of Hs578T cell proliferation that likely mediates this effect through a relatively unique mechanism, suppression of cyclin D3, and not through the AhR. The results suggest that this non-toxic bioflavonoid may be useful as a chemotherapeutic, particularly in combination with agents that target other components of the tumor cell cycle and in situations where estrogen receptor-specific therapeutics are ineffective.
Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells
Authors: Yanochko Gina M , Eckhart Walter 
Published: April 2006

Abstract
Introduction
Activation of the type I insulin-like growth factor receptor (IGFIR) promotes proliferation and inhibits apoptosis in a variety of cell types. Transgenic mice expressing a constitutively active IGFIR or IGF-I develop mammary tumors and increased levels of IGFIR have been detected in primary breast cancers. However, the contribution of IGFIR activation in promoting breast cancer progression remains unknown. Mammary epithelial cell lines grown in three-dimensional cultures form acinar structures that mimic the round, polarized, hollow and growth-arrested features of mammary alveoli. We used this system to determine how proliferation and survival signaling by IGFIR activation affects breast epithelial cell biology and contributes to breast cancer progression.

Methods
Pooled, stable MCF-10A breast epithelial cells expressing wild-type IGFIR or kinase-dead IGFIR (K1003A) were generated using retroviral-mediated gene transfer. The effects of over-expression of wild-type or kinase-dead IGFIR on breast epithelial cell biology were analyzed by confocal microscopy of three-dimensional cultures. The contribution of signaling pathways downstream of IGFIR activation to proliferation and apoptosis were determined by pharmacological inhibition of phosphatidylinositol 3' kinase (PI3K) with LY294002, MAP kinase kinase (MEK) with UO126 and mammalian target of rapamycin (mTOR) with rapamycin.

Results
We found that MCF-10A cells over-expressing the IGFIR formed large, misshapen acinar structures with filled lumina and disrupted apico-basal polarization. This phenotype was ligand-dependent, occurring with IGF-I or supraphysiological doses of insulin, and did not occur in cells over-expressing the kinase-dead receptor. We observed increased proliferation, decreased apoptosis and increased phosphorylation of Ser473 of Akt and Ser2448 of mTOR throughout IGFIR structures. Inhibition of PI3K with LY294002 or MEK with UO126 prevented the development of acinar structures from IGFIR-expressing but not control cells. The mTOR inhibitor rapamycin failed to prevent IGFIR-induced hyperproliferation and survival signaling.

Conclusion
Increased proliferation and survival signaling as well as loss of apico-basal polarity by IGFIR activation in mammary epithelial cells may promote early lesions of breast cancer. Three-dimensional cultures of MCF-10A cells over-expressing the IGFIR are a useful model with which to study the role of IGFIR signaling in breast cancer progression and for characterizing the effects of chemotherapeutics targeted to IGFIR signaling.
A comparison of continuous and bi-level positive airway pressure non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis
Authors: Ho Kwok M , Wong Karen 
Published: April 2006

Abstract
Introduction
We conducted the present study to investigate the potential beneficial and adverse effects of continuous positive airway pressure (CPAP) compared with bi-level positive airway pressure (BiPAP) noninvasive ventilation in patients with cardiogenic pulmonary oedema.

Method
We included randomized controlled studies comparing CPAP and BiPAP treatment in patients with cardiogenic pulmonary oedema from the Cochrane Controlled Trials Register (2005 issue 3), and EMBASE and MEDLINE databases (1966 to 1 December 2005), without language restriction. Two reviewers reviewed the quality of the studies and independently performed data extraction.

Results
Seven randomized controlled studies, including a total of 290 patients with cardiogenic pulmonary oedema, were considered. The hospital mortality (relative risk [RR] 0.76, 95% confidence interval [CI] 0.32–1.78; P = 0.52; I2 = 0%) and risk for requiring invasive ventilation (RR 0.80, 95% CI 0.33–1.94; P = 0.62; I2 = 0%) were not significantly different between patients treated with CPAP and those treated with BiPAP. Stratifying studies that used either fixed or titrated pressure during BiPAP treatment and studies involving patients with or without hypercapnia did not change the results. The duration of noninvasive ventilation required until the pulmonary oedema resolved (weighted mean difference [WMD] in hours = 3.65, 95% CI -12.12 to +19.43; P = 0.65, I2 = 0%) and length of hospital stay (WMD in days = -0.04, 95% CI -2.57 to +2.48; P = 0.97, I2 = 0%) were also not significantly different between the two groups. Based on the limited data available, there was an insignificant trend toward an increase in new onset acute myocardial infarction in patients treated with BiPAP (RR 2.10, 95% CI 0.91–4.84; P = 0.08; I2 = 25.3%).

Conclusion
BiPAP does not offer any significant clinical benefits over CPAP in patients with acute cardiogenic pulmonary oedema. Until a large randomized controlled trial shows significant clinical benefit and cost-effectiveness of BiPAP versus CPAP in patients with acute cardiogenic pulmonary oedema, the choice of modality will depend mainly on the equipment available.
Deciphering cellular states of innate tumor drug responses
Authors: Graudens Esther , Boulanger Virginie , Mollard Cindy , Mariage-Samson Régine , Barlet Xavier , Grémy Guilaine , Couillault Christine , Lajémi Malika , Piatier-Tonneau Dominique , Zaborski Patrick , Eveno Eric , Auffray Charles , Imbeaud Sandrine 
Published: April 2006

Abstract
Background
The molecular mechanisms underlying innate tumor drug resistance, a major obstacle to successful cancer therapy, remain poorly understood. In colorectal cancer (CRC), molecular studies have focused on drug-selected tumor cell lines or individual candidate genes using samples derived from patients already treated with drugs, so that very little data are available prior to drug treatment.

Results
Transcriptional profiles of clinical samples collected from CRC patients prior to their exposure to a combined chemotherapy of folinic acid, 5-fluorouracil and irinotecan were established using microarrays. Vigilant experimental design, power simulations and robust statistics were used to restrain the rates of false negative and false positive hybridizations, allowing successful discrimination between drug resistance and sensitivity states with restricted sampling. A list of 679 genes was established that intrinsically differentiates, for the first time prior to drug exposure, subsequently diagnosed chemo-sensitive and resistant patients. Independent biological validation performed through quantitative PCR confirmed the expression pattern on two additional patients. Careful annotation of interconnected functional networks provided a unique representation of the cellular states underlying drug responses.

Conclusion
Molecular interaction networks are described that provide a solid foundation on which to anchor working hypotheses about mechanisms underlying in vivo innate tumor drug responses. These broad-spectrum cellular signatures represent a starting point from which by-pass chemotherapy schemes, targeting simultaneously several of the molecular mechanisms involved, may be developed for critical therapeutic intervention in CRC patients. The demonstrated power of this research strategy makes it generally applicable to other physiological and pathological situations.