bluuebunny/crossref_metadata_2025 huggingface dataset:
The low-temperature behaviour of cancrinite:an in situ single-crystal X-ray diffraction study
Authors: Gatta G. Diego , Lotti P. , Kahlenberg V. , Haefeker U.
Published: August 2012

The low-temperature structural behaviour of natural cancrinite with a formula Na6.59Ca0.93[Si6.12Al5.88O24](CO3)1.04F0.41·2H2O has been investigated by means of in situ single-crystal X-ray diffraction and Raman spectroscopy. High quality structure refinements were obtained at 293, 250, 220, 180, 140, 100 and at 293 K again (at the end of the low-T experiments). The variation in the unit-cell volume as a function of temperature (T) exhibits a continuous trend, without any evident thermoelastic anomaly. The thermal expansion coefficient αV = (1/V)∂V/∂T is 3.8(7) × 10–5 K–1 (between 100 and 293 K). The structure refinement based on intensity data collected at ambient conditions after the low-T experiment confirmed that the low-T induced deformation processes are completely reversible. The extraframework population does not show significant variations down to 100 K. The strong positional disorder of the carbonate groups along the c axis persists within the T range investigated. The structural behaviour of cancrinite at low-T is mainly governed by the continuous framework rearrangement through the ditrigonalization of the six-membered rings which lie in a plane perpendicular to [0001], the contraction of the four-membered ring joint units, the decrease of the ring corrugation in the (0001) plane, and the flattening of the cancrinite cages. A list of the principal Raman active modes in ambient conditions is provided and discussed.
High-temperature breakdown of the synthetic iodine analogue of vanadinite, Pb5(VO4)3I: an apatite-related compound for iodine radioisotope immobilization?
Authors: Redfern S. A. T. , Smith S. E. , Maddrell E. R.
Published: August 2012

The thermal stability of the synthetic iodine analogue of vanadinite, Pb5(VO4)3I, in air has been investigated by in situ high temperature X-ray powder diffraction between 300 and 1070 K. Rietveld refinement of phase fractions shows that breakdown to lead orthovanadate, Pb3(VO4)2, begins at temperatures above 540 K, with complete loss of iodine above 680 K. More than 50 K below the onset of breakdown, the unit-cell parameters of Pb5(VO4)3I show anomalous contraction in the crystallographic x–y plane (reduction of a) which we associate with movement of iodine within the [0001] channels of the structure. The implications of these results for immobilization of 129I in potential apatite-related crystalline radioactive waste forms are discussed.
The Highwood Mountains potassic igneous province, Montana: mineral fractionation trends and magmatic processes revisited
Authors: Henderson C. M. B. , Richardson F. R. , Charnock J. M.
Published: August 2012

Potassium-rich mafic dykes and lavas from the Highwood Mountains Igneous Province, USA were studied by electron-microprobe and bulk-rock analysis. For the mafic phonolites, compositional trends for olivine and augite phenocrysts and groundmass biotite, alkali feldspar and titanomagnetites are presented and substitution mechanisms discussed. Phenocrysts of biotite and augite in the minettes are also characterized, together with groundmass alkali feldspar and titanomagnetite. The alkali feldspars and biotites are commonly enriched in Ba. Olivine, clinopyroxene and biotite phenocrysts are generally quite magnesium-rich, which is consistent with the primitive natures of the least evolved rocks.

Bulk-rock major-element compositions are combined with modal and microprobe data for the principal phenocrysts to calculate model residual liquid compositions for mafic phonolites, minettes and a syenitic rock. On the basis of phase-equilibria, it is suggested that the main controls of differentiation are polybaric involving crystallization during transport of primary magmas from the mantle for the minettes, and low-pressure differentiation for the mafic phonolites. Whereas magma mixing might have contributed to petrogenesis, many of the disequilibrium features exhibited by clinopyroxene and biotite phenocrysts can also be attributed to pre-existing phenocrysts undergoing decompression melting during magma uprise from its mantle source, followed by rapid crystal growth and episodic volatile loss in sub-volcanic magma chambers.
Combination treatment in vitro with Nutlin, a small-molecule antagonist of MDM2, and pegylated interferon-α 2a specifically targets JAK2V617F-positive polycythemia vera cells
Authors: Lu Min , Wang Xiaoli , Li Yan , Tripodi Joseph , Mosoyan Goar , Mascarenhas John , Kremyanskaya Marina , Najfeld Vesna , Hoffman Ronald
Published: August 2012

Interferon (IFN-α) is effective therapy for polycythemia vera (PV) patients, but it is frequently interrupted because of adverse events. To permit the long-term use of IFN, we propose combining low doses of IFN with Nutlin-3, an antagonist of MDM2, which is also capable of promoting PV CD34+ cell apoptosis. Combination treatment with subtherapeutic doses of Peg IFN-α 2a and Nutlin-3 inhibited PV CD34+ cell proliferation by 50% while inhibiting normal CD34+ cells by 30%. Combination treatment with Nutlin-3 and Peg IFN-α 2a inhibited PV colony formation by 55%-90% while inhibiting normal colony formation by 22%-30%. The combination of these agents also decreased the proportion of JAK2V617F-positive hematopoietic progenitor cells in 6 PV patients studied. Treatment with low doses of Peg IFN-α 2a combined with Nutlin-3 increased phospho-p53 and p21 protein levels in PV CD34+ cells and increased the degree of apoptosis. These 2 reagents affect the tumor suppressor p53 through different pathways with Peg IFN-α 2a activating p38 MAP kinase and STAT1, leading to increased p53 transcription, whereas Nutlin-3 prevents the degradation of p53. These data suggest that treatment with low doses of both Nutlin-3 combined with Peg IFN-α 2a can target PV hematopoietic progenitor cells, eliminating the numbers of malignant hematopoietic progenitor cells.
Development and external validation of a new PTA assessment scale
Authors: Jacobs Bram , van Ekert Janneke , Vernooy Lotje PL , Dieperink Peter , Andriessen Teuntje MJC , Hendriks Marc PH , van Vugt Arie B , Emons Marjolein AA , Borm George F , Vos Pieter E
Published: August 2012

Background

Post-traumatic amnesia (PTA) is a key symptom of traumatic brain injury (TBI). Accurate assessment of PTA is imperative in guiding clinical decision making. Our aim was to develop and externally validate a short, examiner independent and practical PTA scale, by selecting the most discriminative items from existing scales and using a three-word memory test.

Methods

Mild, moderate and severe TBI patients and control subjects were assessed in two separate cohorts, one for derivation and one for validation, using a questionnaire comprised of items from existing PTA scales. We tested which individual items best discriminated between TBI patients and controls, represented by sensitivity and specificity. We then created our PTA scale based on these results. This new scale was externally evaluated for its discriminative value using Receiver Operating Characteristic (ROC) analysis and compared to existing PTA scales.

Results

The derivation cohort included 126 TBI patients and 31 control subjects; the validation cohort consisted of 132 patients and 30 controls. A set of seven items was eventually selected to comprise the new PTA scale: age, name of hospital, time, day of week, month, mode of transport and recall of three words. This scale demonstrated adequate discriminative values compared to existing PTA scales on three consecutive administrations in the validation cohort.

Conclusion

We introduce a valid, practical and examiner independent PTA scale, which is suitable for mild TBI patients at the emergency department and yet still valuable for the follow-up of more severely injured TBI patients.
Filter paper collection of Plasmodium falciparum mRNA for detecting low-density gametocytes
Authors: Jones Sophie , Sutherland Colin J , Hermsen Cornelus , Arens Theo , Teelen Karina , Hallett Rachel , Corran Patrick , van der Vegte-Bolmer Marga , Sauerwein Robert , Drakeley Chris J , Bousema Teun
Published: August 2012

Background

Accurate sampling of sub-microscopic gametocytes is necessary for epidemiological studies to identify the infectious reservoir ofPlasmodium falciparum. Detection of gametocyte mRNA achieves sensitive detection, but requires careful handling of samples. Filter papers can be used for collecting RNA samples, but rigorous testing of their capacity to withstand adverse storage conditions has not been fully explored.

Methods

Three gametocyte dilutions: 10/μL, 1.0/μL and 0.1/μL were spotted onto Whatman™ 903 Protein Saver Cards, FTA Classic Cards and 3MM filter papers that were stored under frozen, cold chain or tropical conditions for up to 13 weeks . RNA was extracted, then detected by quantitative nucleic acid sequence-based amplification (QT-NASBA) and reverse-transcriptase PCR (RT-PCR).

Results

Successful gametocyte detection was more frequently observed from the Whatman 903 Protein Saver Card compared to the Whatman FTA Classic Card, by both techniques (p < 0.0001). When papers were stored at higher temperatures, a loss in sensitivity was experienced for the FTA Classic Card but not the 903 Protein Saver Card or Whatman 3MM filter paper. The sensitivity of gametocyte detection was decreased when papers were stored at high humidity.

Conclusions

This study indicates the Whatman 903 Protein Saver Card is better for Pfs25 mRNA sampling compared to the Whatman FTA Classic Card, and that the Whatman 3MM filter paper may prove to be a satisfactory cheaper option for Pfs25 mRNA sampling. When appropriately dried, filter papers provide a useful approach to Pfs25 mRNA sampling, especially in settings where storage in RNA-protecting buffer is not possible.
Laser-induced inactivation of Plasmodium falciparum
Authors: LeBlanc Danielle , Story Robert , Gross Eitan
Published: August 2012

Background

Haemozoin crystals, produced by Plasmodium during its intra-erythrocytic asexual reproduction cycle, can generate UV light via the laser-induced, non-linear optical process of third harmonic generation (THG). In the current study the feasibility of using haemozoin, constitutively stored in the parasite’s food vacuole, to kill the parasite by irradiation with a near IR laser was evaluated.

Methods

Cultured Plasmodium parasites at different stages of development were irradiated with a pulsed NIR laser and the viability of parasites at each stage was evaluated from their corresponding growth curves using the continuous culture method. Additional testing for germicidal effects of haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to Escherichia coli in suspension. Cell suspensions were then irradiated with the laser and small aliquots taken and spread on agar plates containing selective agents to determine cell viability (CFU).

Results

Parasites in the late-trophozoites form as well as trophozoites in early-stage of DNA synthesis were found to be the most sensitive to the treatment with ~4-log reduction in viability after six passes through the laser beam; followed by parasites in ring phase (~2-log reduction). A ~1-log reduction in E. coli viability was obtained following a 60 min irradiation regimen of the bacteria in the presence of 1 μM synthetic haemozoin and a ~2-log reduction in the presence of 10 μM haemozoin. Minimal (≤15%) cell kill was observed in the presence of 10 μM haemin.

Conclusions

Laser-induced third-harmonic generation by haemozoin can be used to inactivate Plasmodium. This result may have clinical implications for treating severe malaria symptoms by irradiating the patient’s blood through the skin or through dialysis tubing with a NIR laser.
EGF and HB-EGF enhance the proliferation of programmable cells of monocytic origin (PCMO) through activation of MEK/ERK signaling and improve differentiation of PCMO-derived hepatocyte-like cells
Authors: Hyder Ayman , Ehnert Sabrina , Hinz Hebke , Nüssler Andreas K , Fändrich Fred , Ungefroren Hendrik
Published: August 2012

Background

Hepatocyte-like cells (NeoHepatocytes) generated from a peripheral blood monocyte-derived stem cell-like cell (the PCMO) are a promising alternative for primary hepatocytes in cell transplantation studies to cure liver diseases. However, to be therapeutically effective NeoHepatocytes are needed in large quantities. It was the aim of the present study to investigate i) whether the proportion of actively proliferating NeoHepatocytes can be enhanced by supplementing the PCMO differentiation medium (containing M-CSF, IL-3, and human serum) with either EGF or HB-EGF and ii) which signaling pathway underlies the promitotic effect.

Results

EGF and HB-EGF enhanced cell proliferation of PCMOs as demonstrated by increased expression of cycle control genes (ABL, ANAPC2, CDC2, CDK4, CDK6), phosphorylation of the retinoblastoma protein, and increased PCMO cell numbers after stimulation with EGF or HB-EGF. EGF also raised the number of monocytes expressing the proliferation marker Ki67. PCMOs expressed the EGF receptors EGFR (ERBB1) and ERBB3, and expression of both increased during PCMO generation. Phosphoimmunoblotting of PCMOs indicated that both EGF and HB-EGF activated MEK-1/2 and ERK1/2 in a concentration-dependent fashion with the effect of EGF being more prominent. EGF treatment further decreased expression of p47phox and increased that of Nanog indicating enhanced de differentiation and pluripotency, respectively. Treatment with both EGF and HB-EGF resulted in NeoHepatocytes with improved functional parameters.

Conclusions

The results suggested that the addition of EGF or HB-EGF to PCMO differentiation medium superactivates MEK/ERK signaling which then increases both PCMO proliferation, number, and functional differentiation of PCMO-derived NeoHepatocytes.
Untangling the evolution of Rab G proteins: implications of a comprehensive genomic analysis
Authors: Klöpper Tobias H , Kienle Nickias , Fasshauer Dirk , Munro Sean
Published: August 2012

Background

Membrane-bound organelles are a defining feature of eukaryotic cells, and play a central role in most of their fundamental processes. The Rab G proteins are the single largest family of proteins that participate in the traffic between organelles, with 66 Rabs encoded in the human genome. Rabs direct the organelle-specific recruitment of vesicle tethering factors, motor proteins, and regulators of membrane traffic. Each organelle or vesicle class is typically associated with one or more Rab, with the Rabs present in a particular cell reflecting that cell's complement of organelles and trafficking routes.

Results

Through iterative use of hidden Markov models and tree building, we classified Rabs across the eukaryotic kingdom to provide the most comprehensive view of Rab evolution obtained to date. A strikingly large repertoire of at least 20 Rabs appears to have been present in the last eukaryotic common ancestor (LECA), consistent with the 'complexity early' view of eukaryotic evolution. We were able to place these Rabs into six supergroups, giving a deep view into eukaryotic prehistory.

Conclusions

Tracing the fate of the LECA Rabs revealed extensive losses with many extant eukaryotes having fewer Rabs, and none having the full complement. We found that other Rabs have expanded and diversified, including a large expansion at the dawn of metazoans, which could be followed to provide an account of the evolutionary history of all human Rabs. Some Rab changes could be correlated with differences in cellular organization, and the relative lack of variation in other families of membrane-traffic proteins suggests that it is the changes in Rabs that primarily underlies the variation in organelles between species and cell types.
Podosomes in migrating microglia: components and matrix degradation
Authors: Vincent Catherine , Siddiqui Tamjeed A , Schlichter Lyanne C
Published: August 2012

Background

To perform their functions during development and after central nervous system injury, the brain’s immune cells (microglia) must migrate through dense neuropil and extracellular matrix (ECM), but it is not known how they degrade the ECM. In several cancer cell lines and peripheral cells, small multi-molecular complexes (invadopodia in cancer cells, podosomes in nontumor cells) can both adhere to and dissolve the ECM. Podosomes are tiny multi-molecular structures (0.4 to 1 μm) with a core, rich in F-actin and its regulatory molecules, surrounded by a ring containing adhesion and structural proteins.

Methods

Using rat microglia, we performed several functional assays: live cell imaging for chemokinesis, degradation of the ECM component, fibronectin, and chemotactic invasion through Matrigel™, a basement membrane type of ECM. Fluorescent markers were used with high-resolution microscopy to identify podosomes and their components.

Results

The fan-shaped lamella at the leading edge of migrating microglia contained a large F-actin-rich superstructure composed of many tiny (<1 μm) punctae that were adjacent to the substrate, as expected for cell–matrix contact points. This superstructure (which we call a podonut) was restricted to cells with lamellae, and conversely almost every lamella contained a podonut. Each podonut comprised hundreds of podosomes, which could also be seen individually adjacent to the podonut. Microglial podosomes contained hallmark components of these structures previously seen in several cell types: the plaque protein talin in the ring, and F-actin and actin-related protein (Arp) 2 in the core. In microglia, podosomes were also enriched in phosphotyrosine residues and three tyrosine-kinase-regulated proteins: tyrosine kinase substrate with five Src homology 3 domains (Tks5), phosphorylated caveolin-1, and Nox1 (nicotinamide adenine dinucleotide phosphate oxidase 1). When microglia expressed podonuts, they were able to degrade the ECM components, fibronectin, and Matrigel™.

Conclusion

The discovery of functional podosomes in microglia has broad implications, because migration of these innate immune cells is crucial in the developing brain, after damage, and in disease states involving inflammation and matrix remodeling. Based on the roles of invadosomes in peripheral tissues, we propose that microglia use these complex structures to adhere to and degrade the ECM for efficient migration.
Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury
Authors: Bohacek Ivan , Cordeau Pierre , Lalancette–Hébert Mélanie , Gorup Dunja , Weng Yuan-Cheng , Gajovic Srecko , Kriz Jasna
Published: August 2012

Background

Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR) 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs) beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood.

Methods

TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation.

Results

Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1) and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h) were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7) after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1), expressed by microglia in the areas both in and around ischemic lesion.

Conclusion

Our results clearly suggest that optimal and timely microglial activation/innate immune response is needed to limit neuronal damage after stroke.
Sporadic Burkitt lymphomas of children and adolescents in Chinese: a clinicopathological study of 43 cases
Authors: Bi Cheng-Feng , Tang Yuan , Zhang Wen-Yan , Zhao Sha , Wang Xiao-Qing , Yang Qun-Pei , Li Gan-Di , Liu Wei-ping
Published: August 2012

Background

To investigate the clinical and pathologic features as well as the MYC translocations of childhood Burkitt lymphoma (BL) from China.

Methods

Fourty-three cases of childhood BL were retrospectively investigated in morphology, immunophenotype, genotype, treatments and survival analysis.

Results

Clinically, there was a marked male predominance in sex distribution (M: F = 9.75:1); abdomen was the most frequent extranodal sites of involvement (46.5 %), followed by jaws and facial bones (16.3 %). Two third of the patients were in stageI ~ II. Morphologically, 69.76 % of the cases showed classical histologic features, while 30.24 % of them showed greater nuclear pleomorphism in size and shape. Five cases (11.6 %) were positive for EBER1/2. Thirty-one of the 40 cases (77.5 %) had the aberration of IGH/MYC translocation while 7 (17.5 %) had non-IGH/MYC translocation. Thirty patients (69.7 %) received operation and/or chemotherapy while 13 patients (30.3 %) received no treatment. Twenty-seven patients (62.8 %) died of the tumor, 16 alive, with the average survival time 4.9 and 48.7 months respectively. High IPI, advanced clinical stage, increased serum level of LDH and no chemotherapy received as well as tumor size ≥10 cm were related to the lower survival rates of the tumor.

Conclusions

Several differences were showed in this group of BL, including a much higher ratio of male patients, more cases in stageII, clinically inconsistent treatment and a very poor outcome.

Virtual slides

The virtual slide(s) for this article can be found here http://www.diagnosticpathology.diagnomx.eu/vs/1552295877710135
Preeclampsia: a bioinformatics approach through protein-protein interaction networks analysis
Authors: Tejera Eduardo , Bernardes João , Rebelo Irene
Published: August 2012

Background

In this study we explored preeclampsia through a bioinformatics approach. We create a comprehensive genes/proteins dataset by the analysis of both public proteomic data and text mining of public scientific literature. From this dataset the associated protein-protein interaction network has been obtained. Several indexes of centrality have been explored for hubs detection as well as the enrichment statistical analysis of metabolic pathway and disease.

Results

We confirmed the well known relationship between preeclampsia and cardiovascular diseases but also identified statistically significant relationships with respect to cancer and aging. Moreover, significant metabolic pathways such as apoptosis, cancer and cytokine-cytokine receptor interaction have also been identified by enrichment analysis. We obtained FLT1, VEGFA, FN1, F2 and PGF genes with the highest scores by hubs analysis; however, we also found other genes as PDIA3, LYN, SH2B2 and NDRG1 with high scores.

Conclusions

The applied methodology not only led to the identification of well known genes related to preeclampsia but also to propose new candidates poorly explored or completely unknown in the pathogenesis of preeclampsia, which eventually need to be validated experimentally. Moreover, new possible connections were detected between preeclampsia and other diseases that could open new areas of research. More must be done in this area to resolve the identification of unknown interactions of proteins/genes and also for a better integration of metabolic pathways and diseases.
Binding selectivity of dibenzo-18-crown-6 for alkali metal cations in aqueous solution: A density functional theory study using a continuum solvation model
Authors: Choi Chang Min , Heo Jiyoung , Kim Nam Joon
Published: August 2012

Background

Dibenzo-18-crown-6 (DB18C6) exhibits the binding selectivity for alkali metal cations in solution phase. In this study, we investigate the main forces that determine the binding selectivity of DB18C6 for the metal cations in aqueous solution using the density functional theory (DFT) and the conductor-like polarizable continuum model (CPCM).

Results

The bond dissociation free energies (BDFE) of DB18C6 complexes with alkali metal cations (M+-DB18C6, M = Li, Na, K, Rb, and Cs) in aqueous solution are calculated at the B3LYP/6-311++G(d,p)//B3LYP/6-31 + G(d) level using the CPCM. It is found that the theoretical BDFE is the largest for K+-DB18C6 and decreases as the size of the metal cation gets larger or smaller than that of K+, which agrees well with previous experimental results.

Conclusion

The solvation energy of M+-DB18C6 in aqueous solution plays a key role in determining the binding selectivity of DB18C6. In particular, the non-electrostatic dispersion interaction between the solute and solvent, which depends strongly on the complex structure, is largely responsible for the different solvation energies of M+-DB18C6. This study shows that the implicit solvation model like the CPCM works reasonably well in predicting the binding selectivity of DB18C6 in aqueous solution.
Seasonal performance of a malaria rapid diagnosis test at community health clinics in a malaria-hyperendemic region of Burkina Faso
Authors: Diarra Amidou , Nébié Issa , Tiono Alfred , Sanon Souleymane , Soulama Issiaka , Ouédraogo Alphonse , Gansané Adama , Yaro Jean B , Ouédraogo Espérance , Traoré Alfred S , Sirima Sodiomon B
Published: August 2012

Backgound

Treatment of confirmed malaria patients with Artemisinin-based Combination Therapy (ACT) at remote areas is the goal of many anti-malaria programs. Introduction of effective and affordable malaria Rapid Diagnosis Test (RDT) in remote areas could be an alternative tool for malaria case management. This study aimed to assess performance of the OptiMAL dipstick for rapid malaria diagnosis in children under five.

Methods

Malaria symptomatic and asymptomatic children were recruited in a passive manner in two community clinics (CCs). Malaria diagnosis by microscopy and RDT were performed. Performance of the tests was determined.

Results

RDT showed similar ability (61.2%) to accurately diagnose malaria as microscopy (61.1%). OptiMAL showed a high level of sensitivity and specificity, compared with microscopy, during both transmission seasons (high & low), with a sensitivity of 92.9% vs. 74.9% and a specificity of 77.2% vs. 87.5%.

Conclusion

By improving the performance of the test through accurate and continuous quality control of the device in the field, OptiMAL could be suitable for use at CCs for the management and control of malaria.
Evolutionary expansion and functional diversification of oligopeptide transporter gene family in rice
Authors: Liu Tao , Zeng Jiqing , Xia Kuaifei , Fan Tian , Li Yuge , Wang Yaqin , Xu Xinlan , Zhang Mingyong
Published: August 2012

Background

Oligopeptide transporters (OPTs) play important roles in the mobilization of organic nitrogenous compounds and usually associate with tissues that show signs of rapid protein hydrolysis, such as germinating seeds and senescing leaves. This study is to investigate rice OPT genes.

Results

A total of sixteen OsOPT genes (Os for Oryza sative L.) were identified in the rice genome, which were then classified into six sections that belong to two subfamilies (the PT and YSL subfamily). The major mechanisms for evolutionary expansion of the sixteen genes during the rice genome evolution include segmental and tandem duplication. Calculation of the duplication event dates indicated that the sixteen genes originated from nine original OsOPT genes, and the duplication events could be classified into three evolutionary stages. The first evolutionary stage occurred approximately 50 million years ago (Mya) and involved the evolution of four new genes. The second evolutionary stage was approximately 20 Mya and was marked by the appearance of two new genes, and the third evolutionary stage was approximately 9 Mya when two new genes evolved. Mining of the expression database and RT-PCR analysis indicated that the expression of most duplicated OsOPT genes showed high tissue specificities. Diverse expression patterns for the sixteen genes were evaluated using both semi-quantitative RT-PCR and the MPSS data. Expression levels of some OsOPT genes were regulated by abiotic and biotic stresses suggesting the potential involvement of these gene products in rice stress adaptation. Five OsOPT gene mutants showed abnormal development and growth, the primary analysis of five OsOPT gene mutants suggested that they may be necessary for rice development.

Conclusions

These results suggested that rice-specific OsOPT genes might be potentially useful in improving rice.
A single proteolytic cleavage within the lower hinge of trastuzumab reduces immune effector function and in vivo efficacy
Authors: Fan Xuejun , Brezski Randall J , Fa Ming , Deng Hui , Oberholtzer Allison , Gonzalez Anneliese , Dubinsky William P , Strohl William R , Jordan Robert E , Zhang Ningyan , An Zhiqiang
Published: August 2012

Introduction

Recent studies reported that human IgG antibodies are susceptible to specific proteolytic cleavage in their lower hinge region, and the hinge cleavage results in a loss of Fc-mediated effector functions. Trastuzumab is a humanized IgG1 therapeutic monoclonal antibody for the treatment of HER2-overexpressing breast cancers, and its mechanisms of action consist of inhibition of HER2 signaling and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC). The objective of this study is to investigate the potential effect of proteinase hinge cleavage on the efficacy of trastuzumab using both a breast cancer cell culture method and an in vivo mouse xenograft tumor model.

Methods

Trastuzumab antibody was incubated with a panel of human matrix metalloproteinases, and proteolytic cleavage in the lower hinge region was detected using both western blotting and mass spectrometry. Single hinge cleaved trastuzumab (scIgG-T) was purified and evaluated for its ability to mediate ADCC and inhibition of breast cancer cell proliferation in vitro as well as anti-tumor efficacy in the mouse xenograft tumor model. Infiltrated immune cells were detected in tumor tissues by immunohistochemistry.

Results

scIgG-T retains HER2 antigen binding activity and inhibits HER2-mediated downstream signaling and cell proliferation in vitro when compared with the intact trastuzumab. However, scIgG-T lost Fc-mediated ADCC activity in vitro, and had significantly reduced anti-tumor efficacy in a mouse xenograft tumor model. Immunohistochemistry showed reduced immune cell infiltration in tumor tissues treated with scIgG-T when compared with those treated with the intact trastuzumab, which is consistent with the decreased ADCC mediated by scIgG-T in vitro.

Conclusion

Trastuzumab can be cleaved by matrix metalloproteinases within the lower hinge. scIgG-T exhibited a significantly reduced anti-tumor efficacy in vivo due to the weakened immune effector function such as ADCC. The results suggest that the lower hinge cleavage of trastuzumab can occur in the tumor microenvironment where matrix metalloproteinases often have high levels of expression and scIgG-T might compromise its anti-tumor efficacy in the clinic. However, further studies are needed to validate these hypotheses in the clinical setting.
Risk assessment in sepsis: a new prognostication rule by APACHE II score and serum soluble urokinase plasminogen activator receptor
Authors: Giamarellos-Bourboulis Evangelos J , Norrby-Teglund Anna , Mylona Vassiliki , Savva Athina , Tsangaris Iraklis , Dimopoulou Ioanna , Mouktaroudi Maria , Raftogiannis Maria , Georgitsi Marianna , Linnér Anna , Adamis George , Antonopoulou Anastasia , Apostolidou Efterpi , Chrisofos Michael , Katsenos Chrisostomos , Koutelidakis Ioannis , Kotzampassi Katerina , Koratzanis George , Koupetori Marina , Kritselis Ioannis , Lymberopoulou Korina , Mandragos Konstantinos , Marioli Androniki , Sundén-Cullberg Jonas , Mega Anna , Prekates Athanassios , Routsi Christina , Gogos Charalambos , Treutiger Carl-Johan , Armaganidis Apostolos , Dimopoulos George
Published: August 2012

Introduction

Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed.

Methods

A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden.

Results

Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥17 and suPAR ≥12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II <17 and suPAR <12 ng/ml with mortality 5.5%; ii) APACHE II < 17 and suPAR ≥12 ng/ml with mortality 17.4%; iii) APACHE II ≥ 17 and suPAR <12 ng/ml with mortality 37.4%; and iv) APACHE II ≥17 and suPAR ≥12 ng/ml with mortality 51.7%. This prediction rule was confirmed by the Swedish cohort.

Conclusions

A novel prediction rule with four levels of risk in sepsis based on APACHE II score and serum suPAR is proposed. Prognostication by this rule is confirmed by an independent cohort.
First-order systems for elastic and acoustic variable-tilt TI media
Authors: Bube Kenneth P. , Nemeth Tamas , Stefani Joseph P. , Liu Wei , Nihei Kurt T. , Ergas Ray , Zhang Linbin
Published: August 2012

We derive and compare first-order wave propagation systems for variable-tilt elastic and acoustic tilted transversely isotropic (TTI) media. Acoustic TTI systems are commonly used in reverse-time migration. Starting initially with homogeneous vertical transversely isotropic (VTI) media, and then extending to heterogeneous variable-tilt TI media, we derive a pseudoacoustic [Formula: see text] first-order system of differential equations by setting the shear-wave speeds to zero and simplifying the full-elastic system accordingly. This [Formula: see text] system conserves a complete energy, but only when the anelliptic anisotropy parameter [Formula: see text]. For [Formula: see text] (including isotropic media), the system allows linearly time-growing and spatially nonpropagating nonphysical solutions frequently taken for numerical noise. We modified this [Formula: see text] acoustic first-order system by changing the stress variables to obtain a system that stays stable for [Formula: see text]. This system for homogeneous VTI media is generalized to heterogeneous variable-tilt TI media by rotating the stress and strain variables in the full elastic system before setting the shear-wave speeds to zero; the system obtained can be greatly simplified by combining the rotational terms, resulting in only one rotation and extra lower-order terms compared to the [Formula: see text] first-order acoustic system for VTI media. This new system can be simplified further by neglecting the lower-order terms. Both systems (with and without lower-order terms) conserve the same complete energy. Finally, the corresponding [Formula: see text] full elastic system for variable-tilt acoustic TI media can be used for the purposes of benchmarking.
The effect of interface curvature on AVO inversion of near-critical and postcritical PP-reflections
Authors: Skopintseva Lyubov , Aizenberg Arkady , Ayzenberg Milana , Landrø Martin , Nefedkina Tatyana
Published: August 2012

Widely exploited in the industry, amplitude-variation-with-offset (AVO) inversion techniques are based on weak-contrast approximations of the plane-wave reflection coefficients. These approximations are valid for plane waves reflected at almost flat interfaces with weak contrasts in seismic parameters and for reflection angles below the critical angle. Regardless of the underlying assumptions, linearized coefficients provide a simple and physically adequate tool to accurately invert AVO data for seismic parameters at precritical angles. However, the accuracy of linearized coefficients drastically decreases with increasing incidence angle. Limitations occur around and beyond the critical ray, where the effect of wavefront curvature becomes prominent and thus can no more be neglected. The effective reflection coefficients generalize the plane-wave reflection coefficients for waves generated by point sources and reflected at curved interfaces. They account for the wavefront curvature and are adequate at any incidence angle. Our previous studies have shown that including the reflections around and beyond the critical angle in the AVO inversion significantly improves the accuracy of estimated parameters. However, the interface curvature also must have its contribution to the long-offset AVO inversion. We find that the interface curvature affects the energy propagation along the ray tube and the energy diffusion across the ray tube. The energy propagation along the tube is characterized by the geometrical spreading, which is strongly affected by interface curvature. The transverse diffusion is captured by the effective reflection coefficients which are less influenced by interface curvature. The long-offset AVO inversion is thus sensitive to interface curvature through a combination of several wave propagation factors.
Efficient estimation of nonlinear posterior model covariances using maximally sparse cubature rules
Authors: Tompkins Michael J.
Published: August 2012

We estimated posterior model covariances by randomly perturbing data and start model vectors with samples drawn from prior probability distributions, solving the corresponding deterministic inversion for each sample, and integrating the resulting model vectors over all realizations. The computational burden of this method is the number of samples required for the integration because each sample involves a solution to a nonlinear inverse problem. For certain classes of smooth prior probability functions, we present a new approach to the model covariance estimation problem using grids based on maximally sparse cubature integration rules. The [Formula: see text] (degree-two) and [Formula: see text] (degree-three) cubature rules exist to exactly integrate symmetric Gaussian distributions in [Formula: see text] stochastic dimensions. These represent the two sparsest integration rules possible and thus provide the most efficient estimation method for model covariances using integration. In contrast to Monte-Carlo (MC) integration, which requires hundreds of random samples to estimate covariances and has ill-defined convergence, sparse-cubature (quadrature) rules have determined numbers of samples and definite convergence. The trade-off is that they also have limited degrees of accuracy. Using a simple 1D electromagnetic example with 67 stochastic variables, we demonstrated that this sparse integration is three to five times more efficient than MC methods in terms of numbers of required samples.
Numerical modeling analysis of short-offset electric-field measurements with a vertical electric dipole source in complex offshore environments
Authors: Um Evan Schankee , Alumbaugh David L. , Harris Jerry M. , Chen Jiuping
Published: August 2012

We simulated and analyzed short-offset transient electric-field measurements excited by a vertical electric dipole (VED) source over complex 3D offshore models. A finite-element time-domain modeling algorithm was used to efficiently model complex offshore structures. Using a series of cross-sectional snapshots of transient electric fields in the complex offshore models, we examined the characteristics of the short-offset seafloor electric-field measurements. The numerical modeling analysis indicated that the short-offset horizontal electric-field ([Formula: see text]) measurements are very sensitive to subtle multidimensional seafloor topography near a VED source and can show a sign reversal at late times. The sign reversal occurs because the VED source is no longer normal to the seafloor. The occurrence of the sign reversal limits the application of the 1D inversion to the [Formula: see text] measurements, even at a short source-receiver offset. In contrast, the short-offset vertical electric-field ([Formula: see text]) measurements are robust to subtle seafloor topography around the source, and can be interpreted using the 1D inversion. The 1D inversion of the short-offset [Formula: see text] measurements over the complex 3D offshore models shows that the measurements lack the resolution of the thickness and the resistivity of a hydrocarbon reservoir and a salt dome, but can provide useful insights into their lateral extent.
Joint inversion of controlled-source electromagnetic and production data for reservoir monitoring
Authors: Liang Lin , Abubakar Aria , Habashy Tarek M.
Published: August 2012

We present a fluid-flow constrained inversion approach for integrating controlled-source electromagnetic data and production data. In this approach, we assumed that the reservoir model has been well defined from a priori knowledge obtained from other independent measurements such as seismic and/or well-logs. Our objective was to reconstruct the permeability distribution and the shape and location of the flooding front. A finite-difference reservoir simulator was used to model the water-flooding process to simulate the time-dependent production data as well as the temporal and spatial distributions of water saturation and salt concentration, which were then transformed into the reservoir resistivity distribution using a petrophysical relationship. A finite-difference frequency-domain electromagnetic forward-modeling code was then employed to simulate the controlled-source electromagnetic response. The permeability distribution was reconstructed using a multiplicative-regularized Gauss-Newton algorithm for jointly inverting controlled-source electromagnetic and production data. From the water saturation distribution, we can identify the shape and location of the fluid-front resulting from the recovery process.
Focusing the wavefield inside an unknown 1D medium: Beyond seismic interferometry
Authors: Broggini Filippo , Snieder Roel , Wapenaar Kees
Published: August 2012

With seismic interferometry one can retrieve the response to a virtual source inside an unknown medium, if there is a receiver at the position of the virtual source. Using inverse scattering theory, we demonstrate that, for a 1D medium, the requirement of having an actual receiver inside the medium can be circumvented, going beyond seismic interferometry. In this case, the wavefield can be focused inside an unknown medium with independent variations in velocity and density using reflection data only.
Underwater hearing in the loggerhead turtle (Caretta caretta): a comparison of behavioral and auditory evoked potential audiograms
Authors: Martin Kelly J. , Alessi Sarah C. , Gaspard Joseph C. , Tucker Anton D. , Bauer Gordon B. , Mann David A.
Published: August 2012

The purpose of this study was to compare underwater behavioral and auditory evoked potential (AEP) audiograms in a single captive adult loggerhead sea turtle (Caretta caretta). The behavioral audiogram was collected using a go/no-go response procedure and a modified staircase method of threshold determination. AEP thresholds were measured using subdermal electrodes placed beneath the frontoparietal scale, dorsal to the midbrain. Both methods showed the loggerhead sea turtle to have low frequency hearing with best sensitivity between 100 and 400 Hz. AEP testing yielded thresholds from 100 to 1131 Hz with best sensitivity at 200 and 400 Hz (110 dB re. 1 μPa). Behavioral testing using 2 s tonal stimuli yielded underwater thresholds from 50 to 800 Hz with best sensitivity at 100 Hz (98 dB re. 1 μPa). Behavioral thresholds averaged 8 dB lower than AEP thresholds from 100 to 400 Hz and 5 dB higher at 800 Hz. The results suggest that AEP testing can be a good alternative to measuring a behavioral audiogram with wild or untrained marine turtles and when time is a crucial factor.
Glycogen, not dehydration or lipids, limits winter survival of side-blotched lizards (Uta stansburiana)
Authors: Zani Peter A. , Irwin Jason T. , Rollyson Mary E. , Counihan Jessica L. , Healas Sara D. , Lloyd Emily K. , Kojanis Lee C. , Fried Bernard , Sherma Joseph
Published: August 2012

Climate change is causing winters to become milder (less cold and shorter). Recent studies of overwintering ectotherms have suggested that warmer winters increase metabolism and decrease winter survival and subsequent fecundity. Energetic constraints (insufficient energy stores) have been hypothesized as the cause of winter mortality but have not been tested explicitly. Thus, alternative sources of mortality, such as winter dehydration, cannot be ruled out. By employing an experimental design that compared the energetics and water content of lizards that died naturally during laboratory winter with those that survived up to the same point but were then sacrificed, we attempt to distinguish among multiple possible causes of mortality. We test the hypothesis that mortality is caused by insufficient energy stores in the liver, abdominal fat bodies, tail or carcass or through excessive water loss. We found that lizards that died naturally had marginally greater mass loss, lower water content, and less liver glycogen remaining than living animals sampled at the same time. Periodically moistening air during winter reduced water loss, but this did not affect survival, calling into question dehydration as a cause of death. Rather, our results implicate energy limitations in the form of liver glycogen, but not lipids, as the primary cause of mortality in overwintering lizards. When viewed through a lens of changing climates, our results suggest that if milder winters increase the metabolic rate of overwintering ectotherms, individuals may experience greater energetic demands. Increased energy use during winter may subsequently limit individual survival and possibly even impact population persistence.