julilili42/papers huggingface dataset:
Multimodal Elucidation of Choline Metabolism in a Murine Glioma Model Using Magnetic Resonance Spectroscopy and 11C-Choline Positron Emission Tomography
2013-01-24

Abstract The metabolites, transporters, and enzymes involved in choline metabolism are regarded as biomarkers for disease progression in a variety of cancers, but their in vivo detection is not ideal. Both magnetic resonance spectroscopy [MRS using chemical shift imaging (CSI) total choline (tCho)] and 11C-choline positron emission tomography (PET) can probe this pathway, but they have not been compared side by side. In this study, we used the spontaneous murine astrocytoma model SMA560 injected intracranially into syngeneic VM/Dk mice, analyzing animals at various postimplantation time points using dynamic microPET imaging and CSI MRS. We observed an increase in tumor volume and 11C-choline uptake between days 5 and 18. Similarly, tCho levels decreased at days 5 to 18. We found a negative correlation between the tCho and PET results in the tumor and a positive correlation between the tCho tumor-to-brain ratio and choline uptake in the tumor. PCR results confirmed expected increases in expression levels for most of the transporters and enzymes. Using MRS quantification, a good agreement was found between CSI and 11C-choline PET data, whereas a negative correlation occurred when CSI was not referenced. Thus, 11C-choline PET and MRS methods seemed to be complementary in strengths. While advancing tumor proliferation caused an increasing 11C-choline uptake, gliosis and inflammation potentially accounted for a high peritumoral tCho signal in CSI, as supported by histology and secondary ion mass spectrometry imaging. Our findings provide definitive evidence of the use of MRS, CSI, and PET for imaging tumors in vivo. Cancer Res; 73(5); 1470–80. ©2012 AACR.
Fungal host specificity is not a bottleneck for the germination of Pyroleae species (Ericaceae) in a Bavarian forest
2013-01-24

Abstract Plants that produce dust seeds can recruit fungi to meet their earliest requirements for carbon and other nutrients. This germination strategy, termed initial mycoheterotrophy, has been well investigated among the orchid family, but there are numerous other plant lineages that have independently evolved mycoheterotrophic germination strategies. One of these lineages is the tribe P yroleae ( E ricaceae). While the fungi associated with mature plants in Pyroleae have been fairly well documented, their mycobionts at the germination and seedling stages are largely unknown. Here, we use an in situ seed baiting experiment along with molecular fingerprinting techniques and phylogenetic tests to identify the fungi associated with seedlings of two P yroleae species, P yrola chlorantha and O rthilia secunda . Our results indicate that similar to adult plants, Pyroleae seedlings can associate with a suite of ectomycorrhizal fungi. Some seedlings harboured single mycobionts, while others may have been inhabited by multiple fungi. The dominant seedling mycobiont of both P yroleae species was a fungus of unknown trophic status in the order S ebacinales. This taxon was also the only one shared among seedlings of both investigated P yroleae species. We discuss these results juxtaposed to orchids and one additional P yrola species in the context of ontogenetic shifts in fungal host specificity for mycoheterotrophic nutrition.
Plasmonic oligomers in cylindrical vector light beams
2013-01-24

We investigate the excitation as well as propagation of magnetic modes in plasmonic nanostructures. Such structures are particularly suited for excitation with cylindrical vector beams. We study magneto-inductive coupling between adjacent nanostructures. We utilize high-resolution lithographic techniques for the preparation of complex nanostructures consisting of gold as well as aluminium. These structures are subsequently characterized by linear optical spectroscopy. The well characterized and designed structures are afterwards studied in depth by exciting them with radial and azimuthally polarized light and simultaneously measuring their plasmonic near-field behavior. Additionally, we attempt to model and simulate our results, a project which has, to the best of our knowledge, not been attempted so far.
Crystal structure of 1,3-diisopropyl-4,5-dimethylimidazolium oxalic acid monomethyl ester, C14H24N2O4
2013-01-24

Abstract C 14 H 24 N 2 O 4 , monoclinic, P2 1 /n (no. 14), a = 8.1862(8) Å, b = 10.313(1) Å, c = 18.534(2) Å, β = 101.018(8)°, V = 1535.8 Å 3 , Z = 4, R gt (F) = 0.0567, wR ref (F 2 ) = 0.1064, T = 173 K.
Functions, diversity, and evolution of traumatic mating
2013-01-25

ABSTRACT Copulation can involve the wounding of the mating partner by specialised devices. This type of mating, which we term traumatic mating, has been regarded as exceptional. Its prevalence, however, has not been compared across taxa, nor have its functions and putative evolutionary pathways. A categorisation has been lacking to date. We here show that traumatic mating is a widespread and diverse phenomenon that likely evolved via several pathways. Its putative functions include: ( i ) anchorage during mating; ( ii ) stimulation of short‐term female reproductive investment; ( iii ) male paternity advantages; and ( iv ) enhanced fertilisation efficiency in transitions to internal fertilisation. Both natural and sexual selection have likely contributed to the parallel evolution of traumatic intromittent organs in phylogenetically distant taxa. These organs are sometimes remarkably similar in shape and often, but not always, inject sperm. The target sites of trauma infliction and the nature of secretions delivered alongside sperm are thus far poorly studied, but data on both are needed to elucidate the function of traumatic mating. The few existing studies that explicitly quantify fitness impacts of traumatic mating indicate that this strategy may often be costly to the party being wounded. However, a comprehensive approach to assess overall investments and returns for both sexes is a major target for future work. Finally, for the first time, we corroborate quantitatively the hypothesis that traumatic mating evolved relatively more often among hermaphroditic than among gonochoric taxa.
Mutations in POLR3A and POLR3B are a major cause of hypomyelinating leukodystrophies with or without dental abnormalities and/or hypogonadotropic hypogonadism
2013-01-25

Background Leukodystrophies are a heterogeneous group of inherited neurodegenerative disorders characterised by abnormal central nervous system white matter. Mutations in POLR3A and POLR3B genes were recently reported to cause four clinically overlapping hypomyelinating leukodystrophy phenotypes. Our aim was to investigate the presence and frequency of POLR3A and POLR3B mutations in patients with genetically unexplained hypomyelinating leukodystrophies with typical clinical and/or radiologic features of Pol III-related leukodystrophies. Methods The entire coding region and the flanking exon/intron boundaries of POLR3A and/or POLR3B genes were amplified and sequenced in 14 patients. Results Recessive mutations in POLR3A or POLR3B were uncovered in all 14 patients. Eight novel mutations were identified in POLR3A : six missenses, one nonsense, and one frameshift mutation. Seven patients carried compound heterozygous mutations in POLR3B , of whom six shared the common mutation in exon 15 (p.V523E). Seven novel mutations were identified in POLR3B : four missenses, two splice sites, and one intronic mutation. Conclusions To date, our group has described 37 patients, of whom 27 have mutations in POLR3A and 10 in POLR3B, respectively. Altogether, our results further support the proposal that POLR3A and POLR3B mutations are a major cause of hypomyelinating leukodystrophies and suggest that POLR3A mutations are more frequent.
Saxagliptin vs. glipizide as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin alone: long-term (52-week) extension of a 52-week randomised controlled trial
2013-01-25

A lower risk of hypoglycaemia and reduced body weight were observed with saxagliptin vs. glipizide. No other clinically significant differences were observed between groups in safety profile. No significant between-group differences were observed for reductions in glycaemic parameters. After week 24, a smaller weekly rise in HbA1c was observed with saxagliptin vs. glipizide as add-on therapy to metformin.
Docking-Based Virtual Screening of Covalently Binding Ligands: An Orthogonal Lead Discovery Approach
2013-01-25

In pharmaceutical industry, lead discovery strategies and screening collections have been predominantly tailored to discover compounds that modulate target proteins through noncovalent interactions. Conversely, covalent linkage formation is an important mechanism for a quantity of successful drugs in the market, which are discovered in most cases by hindsight instead of systematical design. In this article, the implementation of a docking-based virtual screening workflow for the retrieval of covalent binders is presented considering human cathepsin K as a test case. By use of the docking conditions that led to the best enrichment of known actives, 44 candidate compounds with unknown activity on cathepsin K were finally selected for experimental evaluation. The most potent inhibitor, 4-(N-phenylanilino)-6-pyrrolidin-1-yl-1,3,5-triazine-2-carbonitrile (CP243522), showed a K(i) of 21 nM and was confirmed to have a covalent reversible mechanism of inhibition. The presented approach will have great potential in cases where covalent inhibition is the desired drug discovery strategy.
FAS-Dependent Cell Death in α-Synuclein Transgenic Oligodendrocyte Models of Multiple System Atrophy
2013-01-25

Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention.
Nanoscale Assembly of Paramagnetic Organic Radicals on Au(111) Single Crystals
2013-01-25

Abstract The successful thin‐film deposition of a pyrene‐substituted nitronyl nitroxide radical under controlled conditions has been demonstrated. The electronic properties, chemical environment at the interface, and morphology of the thin films have been investigated by a multitechnique approach. Spectroscopic and morphological analyses indicate a Stranski–Krastanov growth mode and weak physisorption of molecules onto the metallic surface. Electron spin resonance (ESR) spectroscopy shows that evaporation processes and deposition do not affect the paramagnetic character of the molecules. Useful concepts for the engineering of new, purely organic‐based magnets, which may open the way to fruitful exploitation of organic molecular‐beam deposition for assembly on solid surfaces in view of future technological applications, are presented.
Chromosomal instability and bladder cancer: the UroVysion TM test in the UroScreen study
2013-01-25

What's known on the subject? and What does the study add? UroVysion TM is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 locus in exfoliated urothelial cells. This cell‐based test is time‐consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay. Objective To explore changes at chromosomes 3, 7, 17 and 9p21 in order to assess associations with bladder cancer for possible improvements of the UroVysionTM assay regarding screening. Subjects and Methods In all, 1609 men took part in the prospective study UroScreen . Annual screening for bladder cancer was offered to male chemical workers with former exposure to aromatic amines as a voluntary surveillance programme between 2003 and 2010. In all, 191 434 cells in 6517 UroVysion tests were analysed for copy number variations ( CNV ) at chromosome 3, 7, 17 (gains) and 9p21 (deletions) in 1595 men. We assessed CNVs at single or multiple loci using polysomy indices ( PIs , called multiple PI and PI 3, PI 7 and PI 17). We calculated Spearman's rank correlation coefficients (r s ) between these PIs and receiver operating characteristic ( ROC ) curves with areas under the curves ( AUCs ). We applied Cox regression to estimate hazard ratios ( HRs ) to assess the risk of developing bladder cancer. Results Nine out of 21 bladder tumours detected in 20 participants (‘cases’) had a positive UroVysion test, including seven high‐grade carcinomas and seven overlapping results with a positive cytology. Four cases with negative test results did not attend screening annually. No case was found because of a complete loss of 9p21 in at least 12 cells. There were strong correlations between pairwise combinations of gains at chromosome 3, 7 or 17, ranging between r s = 0.98 and r s = 0.99 in cases and between r s = 0.84 and r s = 0.88 in non‐cases ( P &lt; 0.001). Associations were less pronounced with CNVs at 9p21 among cases and were lacking in non‐cases. Estimates of the relative risk of DNA gain for developing a bladder tumour assessed with PIs (threshold 10% of cells) were 47.7 (95% confidence interval [ CI ] 18.3–124.1) for the multiple PI , 44.5 (95% CI 16.5–119.9) for PI 3, 34.7 (95% CI 13.1–92.1) for PI 7 and 52.4 (95% CI 20.7–132.6) for PI 17, as well as 7.9 (95% CI 3.0–20.6) for a complete loss of 9p21 (threshold 2.5% of cells), respectively. ROC analyses showed similar AUCs for multiple PI compared with PIs
DIBARYONS IN NUCLEAR MATTER
2013-01-25

The possibility for occurrence of a Bose condensate of dibaryons in nuclear matter is investigated within the framework of the Walecka model in the mean-field approximation. Constraints for the ω- and σ-meson coupling constants with dibaryons following from the requirement of stability of dibaryon matter against compression are derived and the effect of σ- and π-meson exchange current contributions to the σ-dibaryon coupling constant is discussed. The mean-field solutions of the model are constructed. The effective nucleon mass m ∗ N approaches a critical value ρ c,max DV vanishes when the density of dibaryons ≈ 0.15 fm−3. The Green’s functions of the equilibrium binary mixture of nucleons and dibaryons are constructed by solving the Gorkov-Dyson system of equations in the no-loop approximation. We find that when the square of the sound velocity is positive, the dispersion laws for all elementary
Sensitivity of gastric adenocarcinoma and normal cell lines against combined or conjugated antimetabolites
2013-01-25

The in-vitro growth inhibition of cancer and normal cell lines caused by mixed or covalently linked antimetabolites should clarify whether the conjugation of antimetabolites influences cell sensitivity and growth inhibition in a manner that differs from an equimolar mixture of the same antimetabolites or not. Growth inhibition of the human gastric adenocarcinoma cell lines 23132/87 and MKN-45 in comparison with normal gastric intestinal CCL-241 and the dermal fibroblast cell line NHDF was evaluated using CASY technology. The cell lines were incubated with an equimolar mixture of 5-fluoro-2'-deoxyuridine (5FdU)+3'-C-ethynylcytidine (ECyd) or the covalently linked duplex drug 5FdU(5'→5')ECyd. The drug and metabolites of the assays and medium were determined semiquantitatively using high-performance liquid chromatography. The sensitivity of cancer and nonmalignant cell lines was clearly different against the duplex drug. A measure of 0.65 μmol/l 5FdU(5'→5')ECyd, for example, reduced the growth of MKN-45 or 23132/87 gastric cancer cells from 100% on day 0 to about 50 or 20% on day 10, respectively. However, under the same conditions, the growth of the nonmalignant NHDF and CCL-241 cell lines was not markedly inhibited. The cytostatic activity of the duplex drug is based on the active metabolites in and outside the cell formed by the degradation of 5FdU(5'→5')ECyd. The sensitivity of cell lines against the duplex drug depended on its ability to metabolize the duplex drug. 5FdU(5'→5')ECyd should be more advantageous for specific and efficient polychemotherapy of gastric cancer than the corresponding equimolar mixture of 5FdU+ECyd or a standard combination regime of single drugs.
Molecular Reorganization in Organic Field-Effect Transistors and Its Effect on Two-Dimensional Charge Transport Pathways
2013-01-27

Charge transport in organic thin film transistors takes place in the first few molecular layers in contact with the gate dielectric. Here we demonstrate that the charge transport pathways in these devices are extremely sensitive to the orientational defects of the first monolayers, which arise from specific growth conditions. Although these defects partially heal during the growth, they cause depletion of charge carriers in the first monolayer, and drive the current to flow in the monolayers above the first one. Moreover, the residual defects induce lower crystalline order and charge mobility. These results, which are not intuitively explained by electrostatics arguments, have been obtained by combining in situ real time structural and electrical characterization together with ex situ AFM measurements, on thin films of a relevant n-type organic semiconductor, N,N'-bis(n-octyl)-dicyanoperylene-3,4:9,10-bis dicarboximide grown by sublimation in a quasi-layer-by-layer mode at different substrate temperatures.
Comparison of three methods of cervical measurement in the first trimester: single‐line, two‐line, and tracing
2013-01-27

ABSTRACT Objectives To compare three methods of cervical length measurements using ultrasound in the first trimester: single‐line, two‐line, and tracing. Methods Images appropriate for cervical length measurements were obtained using transvaginal ultrasound between 11 + 0 and 13 + 6 weeks’ gestation. The cervix was measured on stored images using three methods: a single straight line, two segments (two‐line method), and by tracing the distance along the cervical canal. Results were compared for intraoperator repeatability and interoperator variability. The degree of the cervical curvature was measured. Results The mean cervical measurement using the single‐line measurement was 32.8 (SD 4.4) mm. The mean cervical length was essentially the same using the two‐line and tracing measurement: 34.4 (SD 4.7) mm and 34.5 (SD 4.7) mm, respectively. Both intra‐ and interoperator agreement was high. The degree of curvature of the cervical canal was variable, with a resultant variability in the difference between the single straight line measurement and the other two types of measurement. Conclusions Using stored images, each of the measurement techniques is highly reproducible. Both the two‐line and the tracing methods yield larger measurements than the single‐line technique. Therefore, it appears that in select cases the straight line measurement significantly underestimates the actual cervical length. © 2013 John Wiley &amp; Sons, Ltd.
Arachidonoyl-phosphatidylcholine oscillates during the cell cycle and counteracts proliferation by suppressing Akt membrane binding
2013-01-28

The activity of protein kinase B (Akt)—a major kinase promoting cell proliferation and survival—oscillates during the cell cycle. To investigate whether membrane phospholipids may regulate Akt phosphorylation and thus activity, we monitored the lipid profile of nocodazole-synchronized mouse NIH 3T3 fibroblasts during the cell cycle by liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). The proportion of sn -2-arachidonoyl-phosphatidylcholine (20:4-PC) inversely correlated with Akt activity. Increasing the cellular ratio of 20:4-PC by supplementation of 20:4-PC to the cell culture medium diminished Akt [serine (Ser)473] phosphorylation. Saturated and monounsaturated phosphatidylcholines, used as control had no effect; 20:4-PC reduced cell proliferation relative to controls, interfered with S-phase transition, and suppressed Akt downstream signaling and cyclin expression like LY294002, which is a specific inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. Additive effects of 20:4-PC and LY294002 were not observed, underlining the critical role of Akt for 20:4-PC signaling; 20:4-PC suppressed Akt membrane translocation as shown by immunofluorescence microscopy but left the concentration of the anchor lipid phosphatidylinositol-3,4,5-trisphosphate unchanged. An in vitro binding assay suggests that 20:4-PC attenuates the interaction of Akt with its membrane binding site. We conclude that 20:4-PC oscillates during the cell cycle and delays cell cycle progression by inhibiting Akt membrane binding.
Involvement of Toso in activation of monocytes, macrophages, and granulocytes
2013-01-28

Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso −/− mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso −/− mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso −/− mice succumbed to infections of L. monocytogenes , whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock.