bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antinociceptive effects of morphine and naloxone in mu-opioid receptor knockout mice transfected with the MORS196A gene
Authors: Chen Shiou-Lan , Ma Hsin-I , Han Jun-Ming , Lu Ru-Band , Tao Pao-Luh , Law Ping-Yee , Loh Horace H 
Published: April 2010

AbstractBackgroundOpioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development of tolerance and dependence after long-term use, which has limited their clinical use. We previously reported that mutations in the mu-opioid receptors (MOR) S196L and S196A rendered them responsive to the opioid antagonist naloxone without altering the agonist phenotype. In MORS196A knock-in mice, naloxone and naltrexone were antinociceptive but did not cause tolerance or physical dependence. In this study we delivery this mutated MOR gene into pain related pathway to confirm the possibility ofin vivotransfecting MORS196A gene and using naloxone as a new analgesic agent.MethodsThe MOR-knockout (MOR-KO) mice were used to investigate whether morphine and naloxone could show antinociceptive effects when MORS196A gene was transfected into the spinal cords of MOR-KO mice. Double-stranded adeno-associated virus type 2 (dsAAV2) was used to deliver the MORS196A-enhanced green fluorescence protein (EGFP) gene by microinjected the virus into the spinal cord (S2/S3) dorsal horn region. Tail-flick test was used to measure the antinociceptive effect of drugs.ResultsMorphine (10 mg/kg, s.c.) and naloxone (10 mg/kg, s.c.) had no antinociceptive effects in MOR-KO mice before gene transfection. However, two or three weeks after the MOR-S196A gene had been injected locally into the spinal cord of MOR-KO mice, significant antinociceptive effects could be induced by naloxone or morphine. On the other hand, only morphine but not naloxone induced significant tolerance after sub-chronic treatment.ConclusionTransfecting the MORS196A gene into the spinal cord and systemically administering naloxone in MOR-KO mice activated the exogenously delivered mutant MOR and provided antinociceptive effect without causing tolerance. Since naloxone will not activate natural MOR in normal animals or humans, it is expected to produce fewer side effects and less tolerance and dependence than traditional opioid agonists do.
Pelota interacts with HAX1, EIF3G and SRPX and the resulting protein complexes are associated with the actin cytoskeleton
Authors: Burnicka-Turek Ozanna , Kata Aleksandra , Buyandelger Byambajav , Ebermann Linda , Kramann Nadine , Burfeind Peter , Hoyer-Fender Sigrid , Engel Wolfgang , Adham Ibrahim M 
Published: April 2010

Abstract

Background
Pelota (PELO) is an evolutionary conserved protein, which has been reported to be involved in the regulation of cell proliferation and stem cell self-renewal. Recent studies revealed the essential role of PELO in the No-Go mRNA decay, by which mRNA with translational stall are endonucleotically cleaved and degraded. Further, PELO-deficient mice die early during gastrulation due to defects in cell proliferation and/or differentiation.

Results
We show here that PELO is associated with actin microfilaments of mammalian cells. Overexpression of human PELO in Hep2G cells had prominent effect on cell growth, cytoskeleton organization and cell spreading. To find proteins interacting with PELO, full-length human PELO cDNA was used as a bait in a yeast two-hybrid screening assay. Partial sequences of HAX1, EIF3G and SRPX protein were identified as PELO-interacting partners from the screening. The interactions between PELO and HAX1, EIF3G and SRPX were confirmed in vitro by GST pull-down assays and in vivo by co-immunoprecipitation. Furthermore, the PELO interaction domain was mapped to residues 268-385 containing the c-terminal and acidic tail domain. By bimolecular fluorescence complementation assay (BiFC), we found that protein complexes resulting from the interactions between PELO and either HAX1, EIF3G or SRPX were mainly localized to cytoskeletal filaments.

Conclusion
We could show that PELO is subcellularly localized at the actin cytoskeleton, interacts with HAX1, EIF3G and SRPX proteins and that this interaction occurs at the cytoskeleton. Binding of PELO to cytoskeleton-associated proteins may facilitate PELO to detect and degrade aberrant mRNAs, at which the ribosome is stalled during translation.
The Drosophila Fry protein interacts with Trc and is highly mobile in vivo
Authors: Fang Xiaolan , Lu Qiuheng , Emoto Kazou , Adler Paul N 
Published: April 2010

Abstract

Background
Cell polarity is a common feature of eukaryotic cells. The NDR kinases have been found to regulate polarized growth in both animal cells and fungi. Drosophila Tricornered is an NDR kinase that is essential for the normal polarized growth of extensions of epidermal cells and for the tiling and branching of dendrites of da sensory neurons. Tricornered function requires interacting with the large Furry protein (3479 amino acid).

Results
We constructed a furry (fry) transgene and established that it rescued the lethality of fry null mutations. The encoded protein was tagged at both its amino and carboxy termini and this allowed us to demonstrate that the protein existed as an uncleaved protein in vivo. We used the C terminal GFP tag to follow the protein in vivo and found it to be highly mobile. Interestingly Fry accumulated at the distal tip of growing bristles. We established that Fry and Trc could be co-immunoprecipitated from wing discs.

Conclusions
The mobility of Fry in both bristles and dendrites suggests that it could function in directing/mediating the intracellular transport needed for polarized growth. Our observations that full length Fry and Trc show only partial co-localization in growing bristles while an amino terminal fragment of Fry shows close to complete co-localization with Trc suggests that the interaction between these proteins is transient and regulated.
Cell-specific expression of tryptophan decarboxylase and 10-hydroxygeraniol oxidoreductase, key genes involved in camptothecin biosynthesis in Camptotheca acuminata Decne (Nyssaceae)
Authors: Valletta Alessio , Trainotti Livio , Santamaria Anna Rita , Pasqua Gabriella 
Published: April 2010

Abstract

Background

Camptotheca acuminata is a major natural source of the terpenoid indole alkaloid camptothecin (CPT). At present, little is known about the cellular distribution of the biosynthesis of CPT, which would be useful knowledge for developing new strategies and technologies for improving alkaloid production.

Results
The pattern of CPT accumulation was compared with the expression pattern of some genes involved in CPT biosynthesis in C. acuminata [i.e., Ca-TDC1 and Ca-TDC2 (encoding for tryptophan decarboxylase) and Ca-HGO (encoding for 10-hydroxygeraniol oxidoreductase)]. Both CPT accumulation and gene expression were investigated in plants at different degrees of development and in plantlets subjected to drought-stress. In all organs, CPT accumulation was detected in epidermal idioblasts, in some glandular trichomes, and in groups of idioblast cells localized in parenchyma tissues. Drought-stress caused an increase in CPT accumulation and in the number of glandular trichomes containing CPT, whereas no increase in epidermal or parenchymatous idioblasts was observed. In the leaf, Ca-TDC1 expression was detected in some epidermal cells and in groups of mesophyll cells but not in glandular trichomes; in the stem, it was observed in parenchyma cells of the vascular tissue; in the root, no expression was detected. Ca-TDC2 expression was observed exclusively in leaves of plantlets subjected to drought-stress, in the same sites described for Ca-TDC1. In the leaf, Ca-HGO was detected in all chlorenchyma cells; in the stem, it was observed in the same sites described for Ca-TDC1; in the root, no expression was detected.

Conclusions
The finding that the sites of CPT accumulation are not consistently the same as those in which the studied genes are expressed demonstrates an organ-to-organ and cell-to-cell translocation of CPT or its precursors.
Selection of reference genes for quantitative gene expression normalization in flax (Linum usitatissimum L.)
Authors: Huis Rudy , Hawkins Simon , Neutelings Godfrey 
Published: April 2010

Abstract

Background
Quantitative real-time PCR (qRT-PCR) is currently the most accurate method for detecting differential gene expression. Such an approach depends on the identification of uniformly expressed 'housekeeping genes' (HKGs). Extensive transcriptomic data mining and experimental validation in different model plants have shown that the reliability of these endogenous controls can be influenced by the plant species, growth conditions and organs/tissues examined. It is therefore important to identify the best reference genes to use in each biological system before using qRT-PCR to investigate differential gene expression. In this paper we evaluate different candidate HKGs for developmental transcriptomic studies in the economically-important flax fiber- and oil-crop (Linum usitatissimum L).

Results
Specific primers were designed in order to quantify the expression levels of 20 different potential housekeeping genes in flax roots, internal- and external-stem tissues, leaves and flowers at different developmental stages. After calculations of PCR efficiencies, 13 HKGs were retained and their expression stabilities evaluated by the computer algorithms geNorm and NormFinder. According to geNorm, 2 Transcriptional Elongation Factors (TEFs) and 1 Ubiquitin gene are necessary for normalizing gene expression when all studied samples are considered. However, only 2 TEFs are required for normalizing expression in stem tissues. In contrast, NormFinder identified glyceraldehyde-3-phosphate dehydrogenase (GADPH) as the most stably expressed gene when all samples were grouped together, as well as when samples were classed into different sub-groups.
qRT-PCR was then used to investigate the relative expression levels of two splice variants of the flax LuMYB1 gene (homologue of AtMYB59). LuMYB1-1 and LuMYB1-2 were highly expressed in the internal stem tissues as compared to outer stem tissues and other samples. This result was confirmed with both geNorm-designated- and NormFinder-designated-reference genes.

Conclusions
The use of 2 different statistical algorithms results in the identification of different combinations of flax HKGs for expression data normalization. Despite such differences, the use of geNorm-designated- and NormFinder-designated-reference genes enabled us to accurately compare the expression levels of a flax MYB gene in different organs and tissues. Our identification and validation of suitable flax HKGs will facilitate future developmental transcriptomic studies in this economically-important plant.
Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population
Authors: Xiao Mang , Zhang Lei , Zhu Xinhua , Huang Jun , Jiang Huifen , Hu Sunhong , Liu Yuehui 
Published: April 2010

Abstract

Background
The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed TP53 72Arg>Pro and MDM2 309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.

Methods
In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.

Results
We found an increased NPC risk associated with the MDM2 GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).

Conclusion
The findings suggest that polymorphisms of MDM2 and TP53 genes may be genetic modifier for developing NPC.
Regulation of MCP-1 chemokine transcription by p53
Authors: Hacke Katrin , Rincon-Orozco Bladimiro , Buchwalter Gilles , Siehler Simone Y. , Wasylyk Bohdan , Wiesmüller Lisa , Rösl Frank 
Published: April 2010

AbstractBackgroundOur previous studies showed that the expression of the monocyte-chemoattractant protein (MCP)-1, a chemokine, which triggers the infiltration and activation of cells of the monocyte-macrophage lineage, is abrogated in human papillomavirus (HPV)-positive premalignant and malignant cells.In silicoanalysis of the MCP-1 upstream region proposed a putative p53 binding side about 2.5 kb upstream of the transcriptional start. The aim of this study is to monitor a physiological role of p53 in this process.ResultsThe proposed p53 binding side could be confirmedin vitroby electrophoretic-mobility-shift assays andin vivoby chromatin immunoprecipitation. Moreover, the availability of p53 is apparently important for chemokine regulation, since TNF-α can induce MCP-1 only in human keratinocytes expressing the viral oncoprotein E7, but not in HPV16 E6 positive cells, where p53 becomes degraded. A general physiological role of p53 in MCP-1 regulation was further substantiated in HPV-negative cells harboring a temperature-sensitive mutant of p53 and in Li-Fraumeni cells, carrying a germ-line mutation of p53. In both cases, non-functional p53 leads to diminished MCP-1 transcription upon TNF-α treatment. In addition, siRNA directed against p53 decreased MCP-1 transcription after TNF-α addition, directly confirming a crosstalk between p53 and MCP-1.ConclusionThese data support the concept that p53 inactivation during carcinogenesis also affects immune surveillance by interfering with chemokine expression and in turn communication with cells of the immunological compartment.
Isolated pancreatic metastasis from rectal cancer: a case report and review of literature
Authors: Lee Chao-Wei , Wu Ren-Chin , Hsu Jun-Te , Yeh Chun-Nan , Yeh Ta-Sen , Hwang Tsann-Long , Jan Yi-Yin , Chen Miin-Fu 
Published: April 2010

Abstract
Isolated pancreatic metastases from a non-pancreatic primary malignancy are very rare. Studies have shown that resection of metastases is of proven benefit in some types of tumors. We report a case of 76-year-old Taiwanese woman with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and abdominoperineal resection 2 years ago presenting with an asymptomatic mass at the pancreatic tail on a routine follow up abdominal computed tomography scan. The patient underwent distal pancreatectomy and splenectomy under the preoperative impression of a primary pancreatic malignancy. Histological examination of the surgical specimen showed metastatic adenocarcinoma. Immunohistochemical studies confirmed the diagnosis of pancreatic metastasis from rectal adenocarcinoma. Postoperative chemotherapy in the form of oral capecitabine was given. The patient is alive and disease free 12 months after the surgery. In a patient presenting with a pancreatic mass with history of a non-pancreatic malignancy, a differential diagnosis of pancreatic metastasis should be considered. Surgical resection of a solitary pancreatic mass is justified not only to get the definitive diagnosis but also to improve the survival.
Tumor morphological evolution: directed migration and gain and loss of the self-metastatic phenotype
Authors: Enderling Heiko , Hlatky Lynn , Hahnfeldt Philip 
Published: April 2010

Abstract

Background
Aside from the stepwise genetic alterations known to underlie cancer cell creation, the microenvironment is known to profoundly influence subsequent tumor development, morphology and metastasis. Invasive cluster formation has been assumed to be dependent on directed migration and a heterogeneous environment - a conclusion derived from complex models of tumor-environment interaction. At the same time, these models have not included the prospect, now supported by a preponderance of evidence, that only a minority of cancer cells may have stem cell capacity. This proves to weigh heavily on the microenvironmental requirements for the display of characteristic tumor growth phenotypes. We show using agent-based modeling that some defining features of tumor growth ascribed to directed migration might also be realized under random migration, and discuss broader implications for cause-and-effect determination in general.

Results
Considering only the properties of random migration in tumors composed of stem cells and committed cells, we are able to recapitulate a characteristic clustering feature of invasive tumor growth, a property we attribute to "self-metastatic" growth. When the additional influence of directed migrations under chemotactic environments are considered, we find that tumor growth and invasive morphology are supported while the tumor is distant from the source, but are progressively discouraged as the tumor converges about that source.

Conclusions
We show that invasive clustering can derive from basic kinetic assumptions often neglected in more complex models. While higher-order mechanisms, e.g. directed migration upon chemotactic stimuli, may result in clustering growth morphologies, exclusive attributions of this phenotype to this or other structured microenvironments would be inappropriate, in light of our finding these features are observable in a homogeneous environment. Furthermore, directed migration will result in loss of the invasive phenotype as the tumor approaches the attractor source. Reviewers: This article was reviewed by Mark Little and Glen Webb.
Oscillatory dynamics in a model of vascular tumour growth - implications for chemotherapy
Authors: Stamper IJ , Owen MR , Maini PK , Byrne HM 
Published: April 2010

AbstractBackgroundInvestigations of solid tumours suggest that vessel occlusion may occur when increased pressure from the tumour mass is exerted on the vessel walls. Since immature vessels are frequently found in tumours and may be particularly sensitive, such occlusion may impair tumour blood flow and have a negative impact on therapeutic outcome. In order to study the effects that occlusion may have on tumour growth patterns and therapeutic response, in this paper we develop and investigate a continuum model of vascular tumour growth.ResultsBy analysing a spatially uniform submodel, we identify regions of parameter space in which the combination of tumour cell proliferation and vessel occlusion give rise to sustained temporal oscillations in the tumour cell population and in the vessel density. Alternatively, if the vessels are assumed to be less prone to collapse, stable steady state solutions are observed. When spatial effects are considered, the pattern of tumour invasion depends on the dynamics of the spatially uniform submodel. If the submodel predicts a stable steady state, then steady travelling waves are observed in the full model, and the system evolves to the same stable steady state behind the invading front. When the submodel yields oscillatory behaviour, the full model produces periodic travelling waves. The stability of the waves (which can be predicted by approximating the system as one ofλ-ωtype) dictates whether the waves develop into regular or irregular spatio-temporal oscillations. Simulations of chemotherapy reveal that treatment outcome depends crucially on the underlying tumour growth dynamics. In particular, if the dynamics are oscillatory, then therapeutic efficacy is difficult to assess since the fluctuations in the size of the tumour cell population are enhanced, compared to untreated controls.ConclusionsWe have developed a mathematical model of vascular tumour growth formulated as a system of partial differential equations (PDEs). Employing a combination of numerical and analytical techniques, we demonstrate how the spatio-temporal dynamics of the untreated tumour may influence its response to chemotherapy.ReviewersThis manuscript was reviewed by Professor Zvia Agur and Professor Marek Kimmel.
The use of medicinal plants in the trans-himalayan arid zone of Mustang district, Nepal
Authors: Bhattarai Shandesh , Chaudhary Ram P , Quave Cassandra L , Taylor Robin SL 
Published: April 2010

Abstract
Background
This study documents the use of medicinal plants from the Mustang district of the north-central part of Nepal. Traditional botanical medicine is the primary mode of healthcare for most of the population of this district and traditional Tibetan doctors (Amchi) serve as the local medical experts.

Methods
Field research was conducted in 27 communities of the Mustang district in Nepal from 2005-2007. We sampled 202 interviewees, using random and snowball sampling techniques. After obtaining prior informed consent, we collected data through semi-structured interviews and participant-observation techniques. Voucher specimens of all cited botanic species were deposited at TUCH in Nepal.

Results
We recorded the traditional uses of 121 medicinal plant species, belonging to 49 vascular plant and 2 fungal families encompassing 92 genera. These 121 species are employed to treat a total of 116 ailments. We present data on 58 plant species previously unknown for their medicinal uses in the Mustang district. Of the medicinal plants reported, the most common growth form was herbs (73%) followed by shrubs, trees, and climbers. We document that several parts of individual plant species are used as medicine. Plant parts were generally prepared using hot or cold water as the 'solvent', but occasionally remedies were prepared with milk, honey, jaggery, ghee and oil. Amchis recommended different types of medicine including paste, powder, decoction, tablet, pills, infusion, and others through oral, topical, nasal and others routes of administration.

Conclusions
The traditional pharmacopoeia of the Mustang district incorporates a myriad of diverse botanical flora. Traditional knowledge of the remedies is passed down through oral traditions and dedicated apprenticeships under the tutelage of senior Amchi. Although medicinal plants still play a pivotal role in the primary healthcare of the local people of Mustang, efforts to ensure the conservation and sustainable use of medicinal species are necessary.