bluuebunny/crossref_metadata_2025 huggingface dataset:
Opposing roles of polycomb repressive complexes in hematopoietic stem and progenitor cells
Authors: Majewski Ian J. , Ritchie Matthew E. , Phipson Belinda , Corbin Jason , Pakusch Miha , Ebert Anja , Busslinger Meinrad , Koseki Haruhiko , Hu Yifang , Smyth Gordon K. , Alexander Warren S. , Hilton Douglas J. , Blewitt Marnie E.
Published: May 2010

Polycomb group (PcG) proteins are transcriptional repressors with a central role in the establishment and maintenance of gene expression patterns during development. We have investigated the role of polycomb repressive complexes (PRCs) in hematopoietic stem cells (HSCs) and progenitor populations. We show that mice with loss of function mutations in PRC2 components display enhanced HSC/progenitor population activity, whereas mutations that disrupt PRC1 or pleiohomeotic repressive complex are associated with HSC/progenitor cell defects. Because the hierarchical model of PRC action would predict synergistic effects of PRC1 and PRC2 mutation, these opposing effects suggest this model does not hold true in HSC/progenitor cells. To investigate the molecular targets of each complex in HSC/progenitor cells, we measured genome-wide expression changes associated with PRC deficiency, and identified transcriptional networks that are differentially regulated by PRC1 and PRC2. These studies provide new insights into the mechanistic interplay between distinct PRCs and have important implications for approaching PcG proteins as therapeutic targets.
PKCα mediated induction of miR-101 in human hepatoma HepG2 cells
Authors: Chiang Chao-Wei , Huang Yi , Leong Ka-Wai , Chen Lih-Chyang , Chen Hua-Chien , Chen Shu-Jen , Chou Chen-Kung
Published: May 2010

Background

Protein Kinase C (PKC) is a serine/threonine kinase that involved in controlling of many cellular processes such as cell proliferation and differentiation. We have observed previously that TPA (12-O-tetradecanoylphorbol 13-acetate) induces cell cycle arrest in G0/G1 phase in human hepatoma HepG2 cells. However, is there any miRNA involved in PKCα mediated cell growth arrest is still unknown.

Methods

We first surveyed 270 miRNA expression profiles in 20 pairs of human hepatoma tissues. We identified 11 up-regulated and 23 down-regulated miRNAs (FDR < = 0.01; fold-change > = 2) in human hepatoma tissue after Student's T-test and Mann-Whitney rank test. We then examined miRNAs expression profile in TPA treated HepG2 cells. Two miRNAs, miR-101, and miR-29c, were shown to be significantly down regulated in human hepatoma tissues and induced over 4-fold in HepG2 cells under TPA treatment.

Results

In this study, we examined TPA regulated miRNA expression profile in human hepatoma HepG2 cells. We identified two miRNAs, 101 and 29c, were induced by TPA and down regulated in human hepatoma tissues suggest that they might play as tumor suppressor gene and in tumor formation of HCC. Since induction kinetics of miR-101 by TPA was much faster than miR-29c suggests that the induction of miR-101 may be the primary response of TPA treatment. We then further investigated how miR-101 was regulated by TPA. MiR-101 targets two subunits of PRC2 complex, enhancer of zeste homolog 2 (EZH2) and EED, and was shown to play as a tumor suppressor gene in human prostate, breast and liver cancers. The target sequence of miR-101 located in the 3' UTR of both EZH2 and EED's mRNA was identified by bioinformatic analysis and was validated by reporter luciferase activity assay. Then we showed that TPA not only up regulated miR-101 expression, but also reduced protein level of EZH2, EED and H3K27me3 in HepG2 cells. Using lenti-virus-mediated shRNA to knockdown endogenous PKCα expression, we observed that TPA induced growth arrest, elevation of miR-101 and reduction of EZH2, EED and H3K27me3 proteins were all PKCα dependent. Specific inhibitor of ERK completely blocked TPA induced miR-101 expression.

Conclusions

Therefore, this is the first time to show that PKCα and ERK pathway play important role to activate miR-101 expression, reduce PRC2 complex and H3K27me3 level. This epigenetic regulatory pathway may represent a novel mechanism of carcinogenesis and deserve further investigation.
RNA FRABASE 2.0: an advanced web-accessible database with the capacity to search the three-dimensional fragments within RNA structures
Authors: Popenda Mariusz , Szachniuk Marta , Blazewicz Marek , Wasik Szymon , Burke Edmund K , Blazewicz Jacek , Adamiak Ryszard W
Published: May 2010

Background

Recent discoveries concerning novel functions of RNA, such as RNA interference, have contributed towards the growing importance of the field. In this respect, a deeper knowledge of complex three-dimensional RNA structures is essential to understand their new biological functions. A number of bioinformatic tools have been proposed to explore two major structural databases (PDB, NDB) in order to analyze various aspects of RNA tertiary structures. One of these tools is RNA FRABASE 1.0, the first web-accessible database with an engine for automatic search of 3D fragments within PDB-derived RNA structures. This search is based upon the user-defined RNA secondary structure pattern. In this paper, we present and discuss RNA FRABASE 2.0. This second version of the system represents a major extension of this tool in terms of providing new data and a wide spectrum of novel functionalities. An intuitionally operated web server platform enables very fast user-tailored search of three-dimensional RNA fragments, their multi-parameter conformational analysis and visualization.

Description

RNA FRABASE 2.0 has stored information on 1565 PDB-deposited RNA structures, including all NMR models. The RNA FRABASE 2.0 search engine algorithms operate on the database of the RNA sequences and the new library of RNA secondary structures, coded in the dot-bracket format extended to hold multi-stranded structures and to cover residues whose coordinates are missing in the PDB files. The library of RNA secondary structures (and their graphics) is made available. A high level of efficiency of the 3D search has been achieved by introducing novel tools to formulate advanced searching patterns and to screen highly populated tertiary structure elements. RNA FRABASE 2.0 also stores data and conformational parameters in order to provide "on the spot" structural filters to explore the three-dimensional RNA structures. An instant visualization of the 3D RNA structures is provided. RNA FRABASE 2.0 is freely available athttp://rnafrabase.cs.put.poznan.pl.

Conclusions

RNA FRABASE 2.0 provides a novel database and powerful search engine which is equipped with new data and functionalities that are unavailable elsewhere. Our intention is that this advanced version of the RNA FRABASE will be of interest to all researchers working in the RNA field.
Bootstrap-based Support of HGT Inferred by Maximum Parsimony
Authors: Park Hyun Jung , Jin Guohua , Nakhleh Luay
Published: May 2010

Background

Maximum parsimony is one of the most commonly used criteria for reconstructing phylogenetic trees. Recently, Nakhleh and co-workers extended this criterion to enable reconstruction ofphylogenetic networks, and demonstrated its application to detecting reticulate evolutionary relationships. However, one of the major problems with this extension has been that it favors more complex evolutionary relationships over simpler ones, thus having the potential for overestimating the amount of reticulation in the data. Anad hocsolution to this problem that has been used entails inspecting the improvement in the parsimony length as more reticulation events are added to the model, and stopping when the improvement is below a certain threshold.

Results

In this paper, we address this problem in a more systematic way, by proposing a nonparametric bootstrap-based measure of support of inferred reticulation events, and using it to determine the number of those events, as well as their placements. A number of samples is generated from the given sequence alignment, and reticulation events are inferred based on each sample. Finally, the support of each reticulation event is quantified based on the inferences made over all samples.

Conclusions

We have implemented our method in the NEPAL software tool (available publicly athttp://bioinfo.cs.rice.edu/), and studied its performance on both biological and simulated data sets. While our studies show very promising results, they also highlight issues that are inherently challenging when applying the maximum parsimony criterion to detect reticulate evolution.
A mitogenomic perspective on the ancient, rapid radiation in the Galliformes with an emphasis on the Phasianidae
Authors: Shen Yong-Yi , Liang Lu , Sun Yan-Bo , Yue Bi-Song , Yang Xiao-Jun , Murphy Robert W , Zhang Ya-Ping
Published: May 2010

Background

The Galliformes is a well-known and widely distributed Order in Aves. The phylogenetic relationships of galliform birds, especially the turkeys, grouse, chickens, quails, and pheasants, have been studied intensively, likely because of their close association with humans. Despite extensive studies, convergent morphological evolution and rapid radiation have resulted in conflicting hypotheses of phylogenetic relationships. Many internal nodes have remained ambiguous.

Results

We analyzed the complete mitochondrial (mt) genomes from 34 galliform species, including 14 new mt genomes and 20 published mt genomes, and obtained a single, robust tree. Most of the internal branches were relatively short and the terminal branches long suggesting an ancient, rapid radiation. The Megapodiidae formed the sister group to all other galliforms, followed in sequence by the Cracidae, Odontophoridae and Numididae. The remaining clade included the Phasianidae, Tetraonidae and Meleagrididae. The genusArborophilawas the sister group of the remaining taxa followed byPolyplectron. This was followed by two major clades: ((((Gallus,Bambusicola)Francolinus) (Coturnix,Alectoris))Pavo) and (((((((Chrysolophus,Phasianus)Lophura)Syrmaticus)Perdix)Pucrasia) (Meleagris,Bonasa)) ((Lophophorus,Tetraophasis)Tragopan))).

Conclusions

The traditional hypothesis of monophyletic lineages of pheasants, partridges, peafowls and tragopans was not supported in this study. Mitogenomic analyses recovered robust phylogenetic relationships and suggested that the Galliformes formed a model group for the study of morphological and behavioral evolution.
Frequent and recent retrotransposition of orthologous genes plays a role in the evolution of sperm glycolytic enzymes
Authors: Vemuganti Soumya A , de Villena Fernando Pardo-Manuel , O'Brien Deborah A
Published: May 2010

Background

The central metabolic pathway of glycolysis converts glucose to pyruvate, with the net production of 2 ATP and 2 NADH per glucose molecule. Each of the ten reactions in this pathway is typically catalyzed by multiple isozymes encoded by a multigene family. Several isozymes in this pathway are expressed only during spermatogenesis, and gene targeting studies indicate that they are essential for sperm function and male fertility in mouse. At least three of the novel glycolytic isozymes are encoded by retrogenes (Pgk2,Aldoart1, andAldoart2). Their restricted expression profile suggests that retrotransposition may play a significant role in the evolution of sperm glycolytic enzymes.

Results

We conducted a comprehensive genomic analysis of glycolytic enzymes in the human and mouse genomes and identified several intronless copies for all enzymes in the pathway, exceptPfk. Within each gene family, a single orthologous gene was typically retrotransposed frequently and independently in both species. Several retroposed sequences maintained open reading frames (ORFs) and/or provided evidence of alternatively spliced exons. We analyzed expression of sequences with ORFs and <99% sequence identity in the coding region and obtained evidence for the expression of an alternativeGpi1transcript in mouse spermatogenic cells.

Conclusions

Our analysis detected frequent, recent, and lineage-specific retrotransposition of orthologous glycolytic enzymes in the human and mouse genomes. Retrotransposition events are associated with LINE/LTR and genomic integration is random. We found evidence for the alternative splicing of parent genes. Many retroposed sequences have maintained ORFs, suggesting a functional role for these genes.
Epidemiology of Herpes Zoster Infection among Patients Treated in Primary Care Centres in the Valencian Community (Spain)
Authors: Cebrián-Cuenca Ana M , Díez-Domingo Javier , Rodríguez María San-Martín , Puig-Barberá Joan , Navarro-Pérez Jorge ,   the 'Herpes Zoster Research Group of the Valencian Community'
Published: May 2010

Background

There is little available data regarding the epidemiology of herpes zoster (HZ) in Spain. This study's main goal was to estimate the annual incidence of HZ in the Autonomous Community of Valencia.

Methods

From December 1st 2006 to December 1st 2007, a prospective study was carried out in 24 primary health care centres that together provide care for a population of 36,030 persons aged >14 years. We included all adult patients with a clinical diagnosis of HZ who were seen at these centres during the one-year study period. Demographic (i.e., age, gender, and area of residence) and clinical data were also collected from these patients.

Results

A total of 146 cases of HZ were identified during the study period. The annual incidence of HZ was 4.1/1,000 individuals >14 years of age (95% confidence interval [CI]: 3.4-4.7). Cases of HZ were predominantly unilateral and most commonly affected women and people living in rural areas. The most frequently reported symptoms were pain, dysesthesia and itching. A total of 46% of patients also had underlying illnesses (e.g., chronic diseases and/or malignancy) and 24% of patients experienced complications, which were mostly ocular in nature. A total of 91% of patients were treated with antiviral drugs. The median time from symptoms onset to diagnosis was 6.3 days (range: 2.0-8.3).

Conclusions

HZ is a common illness in our region (especially in the older population) that causes a significant clinical burden on primary care providers.
Exploitation of the interaction of measles virus fusogenic envelope proteins with the surface receptor CD46 on human cells for microcell-mediated chromosome transfer
Authors: Katoh Motonobu , Kazuki Yasuhiro , Kazuki Kanako , Kajitani Naoyo , Takiguchi Masato , Nakayama Yuji , Nakamura Takafumi , Oshimura Mitsuo
Published: May 2010

Background

Microcell-mediated chromosome transfer (MMCT) is a technique by which a chromosome(s) is moved from donor to recipient cells by microcell fusion. Polyethylene glycol (PEG) has conventionally been used as a fusogen, and has been very successful in various genetic studies. However, PEG is not applicable for all types of recipient cells, because of its cell type-dependent toxicity. The cytotoxicity of PEG limits the yield of microcell hybrids to low level (10-6 to 10-5 per recipient cells). To harness the full potential of MMCT, a less toxic and more efficient fusion protocol that can be easily manipulated needs to be developed.

Results

Microcell donor CHO cells carrying a human artificial chromosome (HAC) were transfected with genes encoding hemagglutinin (H) and fusion (F) proteins of an attenuated Measles Virus (MV) Edmonston strain. Mixed culture of the CHO transfectants and MV infection-competent human fibrosarcoma cells (HT1080) formed multinucleated syncytia, suggesting the functional expression of the MV-H/F in the CHO cells. Microcells were prepared and applied to HT1080 cells, human immortalized mesenchymal stem cells (hiMSC), and primary fibroblasts. Drug-resistant cells appeared after selection in culture with Blasticidin targeted against the tagged selection marker gene on the HAC. The fusion efficiency was determined by counting the total number of stable clones obtained in each experiment. Retention of the HAC in the microcell hybrids was confirmed by FISH analyses. The three recipient cell lines displayed distinct fusion efficiencies that depended on the cell-surface expression level of CD46, which acts as a receptor for MV. In HT1080 and hiMSC, the maximum efficiency observed was 50 and 100 times greater than that using conventional PEG fusion, respectively. However, the low efficiency of PEG-induced fusion with HFL1 was not improved by the MV fusogen.

Conclusions

Ectopic expression of MV envelope proteins provides an efficient recipient cell-oriented MMCT protocol, facilitating extensive applications for studies of gene function and genetic corrections.
Novel protein kinase D inhibitors cause potent arrest in prostate cancer cell growth and motility
Authors: LaValle Courtney R , Bravo-Altamirano Karla , Giridhar Karthik V , Chen Jun , Sharlow Elizabeth , Lazo John S , Wipf Peter , Wang Q Jane
Published: May 2010

Background

Protein kinase D (PKD) has been implicated in a wide range of cellular processes and pathological conditions including cancer. However, targeting PKD therapeutically and dissecting PKD-mediated cellular responses remains difficult due to lack of a potent and selective inhibitor. Previously, we identified a novel pan-PKD inhibitor, CID755673, with potency in the upper nanomolar range and high selectivity for PKD. In an effort to further enhance its selectivity and potency for potentialin vivoapplication, small molecule analogs of CID755673 were generated by modifying both the core structure and side-chains.

Results

After initial activity screening, five analogs with equal or greater potencies as CID755673 were chosen for further analysis: kb-NB142-70, kb-NB165-09, kb-NB165-31, kb-NB165-92, and kb-NB184-02. Our data showed that modifications to the aromatic core structure in particular significantly increased potency while retaining high specificity for PKD. When tested in prostate cancer cells, all compounds inhibited PMA-induced autophosphorylation of PKD1, with kb-NB142-70 being most active. Importantly, these analogs caused a dramatic arrest in cell proliferation accompanying elevated cytotoxicity when applied to prostate cancer cells. Cell migration and invasion were also inhibited by these analogs with varying potencies that correlated to their cellular activity.

Conclusions

Throughout the battery of experiments, the compounds kb-NB142-70 and kb-NB165-09 emerged as the most potent and specific analogsin vitroand in cells. These compounds are undergoing further testing for their effectiveness as pharmacological tools for dissecting PKD function and as potential anti-cancer agents in the treatment of prostate cancer.
Towards a precise test for malaria diagnosis in the Brazilian Amazon: comparison among field microscopy, a rapid diagnostic test, nested PCR, and a computational expert system based on artificial neural networks
Authors: Andrade Bruno B , Reis-Filho Antonio , Barros Austeclino M , Souza-Neto Sebastião M , Nogueira Lucas L , Fukutani Kiyoshi F , Camargo Erney P , Camargo Luís MA , Barral Aldina , Duarte Ângelo , Barral-Netto Manoel
Published: May 2010

Background

Accurate malaria diagnosis is mandatory for the treatment and management of severe cases. Moreover, individuals with asymptomatic malaria are not usually screened by health care facilities, which further complicates disease control efforts. The present study compared the performances of a malaria rapid diagnosis test (RDT), the thick blood smear method and nested PCR for the diagnosis of symptomatic malaria in the Brazilian Amazon. In addition, an innovative computational approach was tested for the diagnosis of asymptomatic malaria.

Methods

The study was divided in two parts. For the first part, passive case detection was performed in 311 individuals with malaria-related symptoms from a recently urbanized community in the Brazilian Amazon. A cross-sectional investigation compared the diagnostic performance of the RDT Optimal-IT, nested PCR and light microscopy. The second part of the study involved active case detection of asymptomatic malaria in 380 individuals from riverine communities in Rondônia, Brazil. The performances of microscopy, nested PCR and an expert computational system based on artificial neural networks (MalDANN) using epidemiological data were compared.

Results

Nested PCR was shown to be the gold standard for diagnosis of both symptomatic and asymptomatic malaria because it detected the major number of cases and presented the maximum specificity. Surprisingly, the RDT was superior to microscopy in the diagnosis of cases with low parasitaemia. Nevertheless, RDT could not discriminate the Plasmodium species in 12 cases of mixed infections (Plasmodium vivax + Plasmodium falciparum). Moreover, the microscopy presented low performance in the detection of asymptomatic cases (61.25% of correct diagnoses). The MalDANN system using epidemiological data was worse that the light microscopy (56% of correct diagnoses). However, when information regarding plasma levels of interleukin-10 and interferon-gamma were inputted, the MalDANN performance sensibly increased (80% correct diagnoses).

Conclusions

An RDT for malaria diagnosis may find a promising use in the Brazilian Amazon integrating a rational diagnostic approach. Despite the low performance of the MalDANN test using solely epidemiological data, an approach based on neural networks may be feasible in cases where simpler methods for discriminating individuals below and above threshold cytokine levels are available.
Low titers of measles antibody in mothers whose infants suffered from measles before eligible age for measles vaccination
Authors: Zhao Hong , Lu Pei-Shan , Hu Yali , Wu Qiaozhen , Yao Wenhu , Zhou Yi-Hua
Published: May 2010

Background

Resurgence or outbreak of measles recently occurred in both developed and developing countries despite long-standing widespread use of measles vaccine. Measles incidence in China has increased since 2002, particularly in infants and in persons ≥ 15 years of age. It is speculated that infants may acquire fewer measles IgG from their mothers, resulting in the reduced duration of protection during their early months of life. This study aimed to clarify the reason of increased susceptibility to measles in young infants in China. Measles IgG in 24 measles infants ≤ 9 months of age and their vaccinated mothers was quantitatively measured. The mean measles neutralizing titer in the vaccinated mothers and in 13 age-match women with the histories of clinical measles were compared.

Results

All the mothers were confirmed to be vaccinated successfully by the presence of measles IgG. Six vaccinated mothers were positive for measles IgM and had high concentrations of measles IgG and the neutralizing antibody, indicating underwent natural boosting. The mean measles neutralizing titer in 18 vaccinated mothers without natural boosting were significantly lower than that in 13 age-match women with the histories of clinical measles (1:37 vs 1:182, P < 0.05).

Conclusions

Our results suggest that infants born to mothers who acquired immunity to measles by vaccination may get a relatively small amount of measles antibody, resulting in loss of the immunity to measles before the vaccination age. Measures to improve the immunity in young infants not eligible for measles vaccination would be critical to interrupt the measles transmission in China.
Challenges in experimental data integration within genome-scale metabolic models
Authors: Bourguignon Pierre-Yves , Samal Areejit , Képès François , Jost Jürgen , Martin Olivier C
Published: May 2010

A report of the meeting "Challenges in experimental data integration within genome-scale metabolic models", Institut Henri Poincaré, Paris, October 10-11 2009, organized by the CNRS-MPG joint program in Systems Biology.
Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients
Authors: Macedo Etienne , Bouchard Josée , Soroko Sharon H , Chertow Glenn M , Himmelfarb Jonathan , Ikizler T Alp , Paganini Emil P , Mehta Ravindra L ,   for the Program to Improve Care in Acute Renal Disease (PICARD) study
Published: May 2010

Introduction

Serum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.

Methods

In 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours.

Results

The median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression.

Conclusions

In critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.
Molecular chaperones and protein-folding catalysts as intercellular signaling regulators in immunity and inflammation
Authors: Henderson Brian , Pockley A Graham
Published: May 2010

Review critically examines the hypothesis that molecular chaperones from prokaryotic and eukaryotic sources can be secreted by cells and function as intercellular signaling molecules.

This review critically examines the hypothesis that molecular chaperones and protein-folding catalysts from prokaryotes and eukaryotes can be secreted by cells and function as intercellular signals, principally but not exclusively, for leukocytes. A growing number of molecular chaperones have been reported to function as ligands for selected receptors and/or receptors for specific ligands. Molecular chaperones initially appeared to act primarily as stimulatory signals for leukocytes and thus, were seen as proinflammatory mediators. However, evidence is now emerging that molecular chaperones can have anti-inflammatory actions or, depending on the protein and concentration, anti- and proinflammatory functions. Recasting the original hypothesis, we propose that molecular chaperones and protein-folding catalysts are “moonlighting” proteins that function as homeostatic immune regulators but may also under certain circumstances, contribute to tissue pathology. One of the key issues in the field of molecular chaperone biology relates to the role of microbial contaminants in their signaling activity; this too will be evaluated critically. The most fascinating aspect of molecular chaperones probably relates to evidence for their therapeutic potential in human disease, and ongoing studies are evaluating this potential in a range of clinical settings.
Presenting seismic stratigraphy and attribute analysis as pioneer techniques for delineation of reservoir quality sand bodies in the Indus Offshore Basin, southwest Pakistan
Authors: Sattar Nauman , Khan Farhan A. , Farid Asam , Khan Amjad A. , Hasnain Kashif , Shabih Mohammad
Published: May 2010

It is generally believed that various exploration failures in the offshore areas of Pakistan are due to the absence of a mature petroleum system. However, a few recent gas shows and shales with 0.55–3.24% TOC suggest that a Middle-Upper Miocene lowstand systems tract (LST) exists that possesses organic, paleo-environmental, and sequence stratigraphic characteristics of a potential source rock. The objective of this work was to highlight and delineate the slope and basin facies through seismic sequence stratigraphy and seismic attribute analysis as a new approach to the interpretation of the southwestern Lower Indus Basin of Pakistan. Working within a sequence stratigraphic framework, four sequences have been delineated on the basis of reflection termination patterns. A sea-level curve was constructed from the reflection patterns representing coastal onlap. This sea-level curve was compared to a hypothetical sea-level curve generated by a spectral analysis Fourier transform function on the density logs.
AVO ritualization and functionalism (then and now)
Authors: Ross Christopher P.
Published: May 2010

A day laborer, trying to surprise his new wife, saves his spare change and works extra hours in effort to afford a beautiful roast for the holidays. The night before the holiday he stops at the butcher shop on his way home from work and purchases the roast and surprises his wife. She kisses him, excitedly takes the roast into the kitchen, unwraps it, puts it on the counter, and with a large meat cleaver trims one-quarter of the roast off both ends and discards it in the trash before placing the meat in a large pan for further preparation.
Detangling geologic imprints on depth uncertainty: A method for analyzing overburden effects on depth prediction
Authors: Unger Mike
Published: May 2010

Captain Field is a large heavy-oil accumulation in block 13/22a of the Inner Moray Firth province of the UK sector of the North Sea (Figure 1). The field is operated by Chevron Upstream Europe, with the Korean Captain Company Limited (KCCL) as a partner.
Bayesian lithology/fluid prediction constrained by spatial couplings and rock physics depth trends
Authors: Rimstad Kjartan , Avseth Per , Omre Henning
Published: May 2010

Elastic properties of rocks are strongly influenced by geological trends, and the uncertainties in the lithology/fluids prediction can be reduced if these trends are included in the inversion model. In this study lithology/fluid classification constrained by depth trends (Avseth et al., 2003) is considered in a spatial setting with a Markov random field prior model for spatial coupling of the discrete lithology/fluids classes.
Bias in geophysical interpretation–the case for multiple deterministic scenarios
Authors: Rowbotham Peter , Kane Peter , Bentley Mark
Published: May 2010

Oil exploration and production business decisions need accurate forecasts derived from a description of the subsurface combined with a statement of the uncertainty associated with that description. However, we commonly observe biases in the quantification of uncertainty due to cultural influence and overconfidence in our ability to estimate uncertainty, leading to disappointment when reality lies outside predictions. In tandem, a lack of insight into the value that uncertainty holds on the business case can lead to a mismatch between the effort expended on deriving a single “best” guess versus that on understanding the uncertainty range associated with that guess. Generating stochastic results around a “best technical case” can give a seemingly plausible range of uncertainty but typically fails to explore the uncertainty space.
The rational geoscientist
Authors: Hall Matt
Published: May 2010

That intuition can lead us astray is obvious and well-known, but watch for examples of people relying on intuition to solve a problem and you will see it everywhere. When people talk of a hunch or gut feeling, they're talking about using their intuition.
Glucolipotoxicity Alters Lipid Partitioning and Causes Mitochondrial Dysfunction, Cholesterol, and Ceramide Deposition and Reactive Oxygen Species Production in INS832/13 ß-Cells
Authors: El-Assaad Wissal , Joly Erik , Barbeau Annie , Sladek Robert , Buteau Jean , Maestre Isabel , Pepin Emilie , Zhao Shangang , Iglesias José , Roche Enrique , Prentki Marc
Published: May 2010

Elevated glucose and saturated fatty acids synergize in inducing apoptosis in INS832/13 cells and in human islet cells. In order to gain insight into the molecular mechanism(s) of glucolipotoxicity (Gltox), gene profiling and metabolic analyses were performed in INS832/13 cells cultured at 5 or 20 mm glucose in the absence or presence of palmitate. Expression changes were observed for transcripts involved in mitochondrial, lipid, and glucose metabolism. At 24 h after Gltox, increased expression of lipid partitioning genes suggested a promotion of fatty acid esterification and reduced lipid oxidation/detoxification, whereas changes in the expression of energy metabolism genes suggested mitochondrial dysfunction. These changes were associated with decreased glucose-induced insulin secretion, total insulin content, ATP levels, AMP-kinase activity, mitochondrial membrane potential and fat oxidation, unchanged de novo fatty acid synthesis, and increased reactive oxygen species, cholesterol, ceramide, and triglyceride levels. However, the synergy between elevated glucose and palmitate to cause ß-cell toxicity in term of apoptosis and reduced glucose-induced insulin secretion only correlated with triglyceride and ceramide depositions. Overexpression of endoplasmic reticulum glycerol-3-phosphate acyl transferase to enhance lipid esterification amplified Gltox at intermediate glucose (11 mm), whereas reducing acetyl-coenzyme A carboxylase 1 expression by small interfering RNA to shift lipid partitioning to fat oxidation reduced Gltox. The results suggest that Gltox entails alterations in lipid partitioning, sterol and ceramide accumulation, mitochondrial dysfunction, and reactive oxygen species production, all contributing to altering ß-cell function. The data also suggest that the early promotion of lipid esterification processes is instrumental in the Gltox process.
Interaction of Adenosine 3′,5′-Cyclic Monophosphate and Tumor Necrosis Factor-α on Serum Amyloid A3 Expression in Mouse Granulosa Cells: Dependence on CCAAT-Enhancing Binding Protein-β Isoform
Authors: Son Deok-Soo , Terranova Paul F. , Roby Katherine F.
Published: May 2010

TNFα is an inflammatory-related cytokine that has inhibitory effects on gonadotropin- and cAMP-stimulated steroidogenesis and folliculogenesis. Because ovulation is an inflammatory reaction and TNF specifically induces serum amyloid A3 (SAA3) in mouse granulosa cells, the effect of cAMP on TNF-induced SAA3 promoter activity, mRNA and protein was investigated. Granulosa cells from immature mice were cultured with TNF and/or cAMP. TNF increased SAA3 promoter activity, mRNA, and protein, which were further increased by cAMP. cAMP alone increased SAA3 promoter activity, but SAA3 mRNA and protein remained undetectable. Thus, there appeared to be different mechanisms by which TNF and cAMP regulated SAA3 expression. SAA3 promoters lacking a nuclear factor (NF)-κB-like site or containing its mutant were not responsive to TNF but were responsive to cAMP. Among four CCAAT-enhancing binding protein (C/EBP) sites in the SAA3 promoter, the C/EBP site nearest the NF-κB-like site was required for TNF-induced SAA3. The C/EBP site at −75/−67 was necessary for responsiveness to cAMP. Dominant-negative C/EBP and cAMP response element-binding protein or short interfering RNA of C/EBPβ blocked TNF- or cAMP-induced SAA3 promoter activity. The combination of TNF and cAMP increased C/EBPβ protein above that induced by TNF or cAMP alone. Thus, cAMP in combination with TNF specifically induced C/EBPβ protein, leading to enhanced SAA3 expression but requiring NF-κB in mouse granulose cells. In addition, like TNF, SAA inhibited cAMP-induced estradiol accumulation and CYP19 levels. These data indicate SAA may play a role in events occurring during the ovulation process.
Strain-Specific Defects in Testicular Development and Sperm Epigenetic Patterns in 5,10-Methylenetetrahydrofolate Reductase-Deficient Mice
Authors: Chan Donovan , Cushnie Duncan W. , Neaga Oana R. , Lawrance Andrea K. , Rozen Rima , Trasler Jacquetta M.
Published: May 2010

Methylenetetrahydrofolate reductase (MTHFR) is a crucial folate pathway enzyme that contributes to the maintenance of cellular pools of S-adenosylmethionine, the universal methyl donor for several reactions including DNA methylation. Whereas Mthfr−/− BALB/c mice show growth retardation, developmental delay, and spermatogenic defects and infertility, C57BL/6 mice appear to have a less severe phenotype. In the present study, we investigated the effects of MTHFR deficiency on early germ cell development in both strains and assessed whether MTHFR deficiency results in DNA methylation abnormalities in sperm. The reproductive phenotype associated with MTHFR deficiency differed strikingly between the two strains, with BALB/c mice showing an early postnatal loss of germ cell number and proliferation that was not evident in the C57BL/6 mice. As a result, the BALB/c MTHFR-deficient mice were infertile, whereas the C57BL/6 mice had decreased sperm numbers and altered testicular histology but showed normal fertility. Imprinted genes and sequences that normally become methylated during spermatogenesis were unaffected by MTHFR deficiency in C57BL/6 mice. In contrast, a genome-wide restriction landmark genomic scanning approach revealed a number of sites of hypo- and hypermethylation in the sperm of this mouse strain. These results showing strain-specific defects in MTHFR-deficient mice may help to explain population differences in infertility among men with common MTHFR polymorphisms.
Transient Expression of Interferon-Inducible p204 in the Early Stage Is Required for Adipogenesis in 3T3-L1 Cells
Authors: Xiao Jing , Sun Bing , Cai Guo-ping
Published: May 2010

A member of the interferon-inducible p200 family of proteins, p204, has recently been reported to function in the development of many mesoderm-derived tissues, such as bone, muscle, and cartilage. However, no published study has yet investigated the role of p204 in adipogenesis. Our preliminary experiments showed that p204 can be found in 3T3-L1 preadipocytes, and its expression was up-regulated in a differentiation-dependent manner. As such, we hypothesized that p204 is associated with adipogenesis and focused on the influence of p204 on adipogenesis. In the present study, we investigated the transient elevated expression and cytoplasm-to-nucleus translocation of p204 in the early stage of adipogenesis. To determine the effect of p204 on adipogenesis, p204-siRNA and expression vector were produced for p204 suppression and overexpression, respectively. The knockdown of p204 resulted in a significantly depressed adipocyte differentiation, whereas p204 overexpression promoted adipocyte differentiation. The mRNA expression of adipogenic markers, such as peroxisome-proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding-protein (C/EBP)α, lipoprotein lipase, and adipsin, was decreased by p204 suppression and increased by p204 overexpression. A coimmunoprecipitation assay coupled with an indirect immunofluorescence assay also indicated that p204 interacted and colocalized with C/EBPδ in the nucleus. Furthermore, the knockdown of p204 disrupted the interaction between p204 and C/EBPδ and partially suppressed the PPARγ transcriptional activity by dissociating C/EBPδ with the PPARγ promoter element. Collectively, our data indicate that the transient expression of p204 in the early stage is indispensable for adipocyte differentiation. Disruption of p204 expression patterns at this stage leads to irreversible damage in fat formation.
Distributed Forebrain Sites Mediate Melatonin-Induced Short-Day Responses in Siberian Hamsters
Authors: Leitner Claudia , Bartness Timothy J.
Published: May 2010

The pineal hormone melatonin (MEL) is the key initiator in regulating seasonal photoperiodic responses; however, the central sites that mediate short day (SD) winter-like responses, such as testicular regression and decreases in white adipose tissue (WAT) mass, by Siberian hamsters are not precisely known. WAT is innervated by the sympathetic nervous system, and several forebrain sites that are part of the sympathetic nervous system outflow to WAT coexpress MEL1a receptor mRNA [e.g. suprachiasmatic nucleus, subzona incerta (SubZi), dorsomedial nucleus of the hypothalamus, nucleus reunions and paraventricular nuclei of the thalamus]. We tested the involvement of these sites in MEL-triggered SD responses. A long duration, SD-like MEL signal was applied site specifically for 5 wk, with sc and third ventricle MEL application serving as positive controls. Whereas SD MEL signals delivered to each of these sites were able to induce testicular regression, all but the paraventricular nuclei of the thalamus also trigger SD-induced decreases in body mass. Third ventricle, sc, suprachiasmatic nucleus, or SubZi MEL application also decreased WAT mass, and only sc and SubZi MEL application decreased food intake. Collectively these data suggest a distributed system of MEL-sensitive brain sites sufficient to mediate these SD responses, the redundancy of which suggests its importance for appropriate seasonal responses critical for overwintering.
Inducible Nitric Oxide Synthase Deficiency in Myeloid Cells Does Not Prevent Diet-Induced Insulin Resistance
Authors: Lu Min , Li PingPing , Pferdekamper Jan , Fan WuQiang , Saberi Maziyar , Schenk Simon , Olefsky Jerrold M.
Published: May 2010

Recent findings denote an important contribution of macrophage inflammatory pathways in causing obesity-related insulin resistance. Inducible nitric oxide synthase (iNOS) is activated in proinflammatory macrophages and modestly elevated in insulin-responsive tissues. Although the benefits of systemic iNOS inhibition in insulin-resistant models have been demonstrated, the role of macrophage iNOS in metabolic disorders is not clear. In the current work, we used bone marrow transplantation (BMT) to generate mice with myeloid iNOS deficiency [iNOS BMT knockout (KO)]. Interestingly, disruption of iNOS in myeloid cells did not protect mice from high-fat diet-induced obesity and insulin resistance. When mice were treated with the iNOS inhibitor, N6-(1-Iminoethyl)-L-lysine hydrochloride (L-NIL), we observed a significant and comparable improvement of glucose homeostasis and insulin sensitivity in both wild-type and iNOS BMT KO mice. We further demonstrated that absence of iNOS in primary macrophages did not affect acute TLR4 signaling pathways and had only a modest and mixed effect on inflammatory gene expression. With respect to TNFα treatment, iNOS KO macrophages showed, if anything, a greater inflammatory response. In summary, we conclude that iNOS inhibition in tissues other than myeloid cells is responsible for the beneficial effects in obesity/insulin resistance.
An Efficient and Highly Regioselective Cycloaddition of Aryl Isocyanates with Oxiranes Promoted by MgI2 Etherate
Authors: Zhang Xingxian , Chen Wei
Published: May 2010

Cycloaddition of various aryl isocyanates with oxiranes was realized in the presence of 50 mol % MgI2 etherate in a mild, efficient, and highly regioselective manner, which afforded 3-aryloxazolidin-2-one. Solvents (i.e., THF) and amounts of MgI2 etherate catalyst played the critical roles for the unique reactivity of this catalytic system.
Procedures required of sponsors prior to embarking on clinical trials in humans
Authors:   Medicines and Healthcare products Regulatory Agency
Published: May 2010

When embarking on a clinical trial of an investigational medicinal product (IMP) for the first time in humans, the risks associated with the administration of the compound must be identified and mitigated accordingly. This article outlines some of the guidance sponsors should consider when designing a first-in-human trial. The procedures in the UK for trials using higher risk compounds and MHRA accreditation of Phase 1 units is also discussed.
Rhenium- and manganese-catalyzed carbon–carbon bond formation using 1,3-dicarbonyl compounds and alkynes
Authors: Kuninobu Yoichiro , Kawata Atsushi , Yudha Salprima S. , Takata Hisatsugu , Nishi Mitsumi , Takai Kazuhiko
Published: May 2010

A rhenium complex, [ReBr(CO)3(thf)]2, catalyzed insertion of terminal alkynes into a C–H bond of active methylene sites of 1,3-dicarbonyl compounds. When a catalytic amount of isocyanide or molecular sieves was added to the reaction mixture, the reaction course changed markedly, and insertion of alkynes into a C–C single bond between α- and β-positions of cyclic and acyclic β-keto esters occurred. The formed acyclic δ-keto esters could be converted to 2-pyranones, which were applied to the synthesis of multisubstituted aromatic compounds via the Diels–Alder reaction and successive elimination of carbon dioxide. In the case of the rhenium-catalyzed reactions between terminal alkynes and β-keto esters without substituent at the α-position, tetrasubstituted benzenes were produced regioselectively by two-to-one reaction of the components. The yields of tetrasubstituted benzenes were improved by using a manganese catalyst.
Reproductive-endocrine point-of-care testing: current status and limitations
Authors: Cervinski Mark A. , Gronowski Ann M.
Published: May 2010

Point-of-care (POC) testing for the detection of pregnancy and the prediction of ovulation has grown and evolved since the introduction of the first qualitative pregnancy test marketed directly to the consumer over three decades ago. Numerous publications have analyzed both pregnancy and ovulation prediction devices for their sensitivity, accuracy and general utility. Despite vast improvements in ease-of-use and sensitivity from their earlier forms, the primary literature regarding the utility of these devices is at times incomplete. This article reviews the literature focusing on the sensitivity and accuracy of the modern urine-luteinizing hormone ovulation prediction devices, and the effect these devices have on fertility rates. In addition, the analytical sensitivity and clinical utility of POC pregnancy tests will be reviewed, along with the potential causes of false negative and false positive results.

Clin Chem Lab Med 2010;48:935–42.
Neutrophil gelatinase-associated lipocalin (NGAL) for acute kidney injury – the renal troponin?1
Authors: Haase Michael , Haase-Fielitz Anja
Published: May 2010

Acute kidney injury (AKI) is a frequent complication of hospitalized patients and associated with significantly increased morbidity and mortality. Probably, the delay in the diagnosis of AKI resulting from currently available renal function markers, such as serum creatinine contributes to the fact that to date, no simple, safe, and effective intervention to prevent or successfully treat AKI in the general patient population has been found. At the time of diagnosis of established AKI, irreversible organ damage might already have occurred. Neutrophil gelatinase-associated lipocalin (NGAL) is a protease-resistant polypeptide, which is released from the distal nephron in response to ischemic, toxic, or inflammatory insult to the kidney. Available data suggest NGAL to be an early and predictive biomarker for AKI. Novel renal biomarkers indicating cellular/tissue damage might guide patient-tailored earlier initiation of nephroprotection or withdrawal of nephrotoxins directed at improvement of outcomes in patients developing AKI.
Tumor markers for bladder cancer: outlook for routine use1
Authors: Ecke Thorsten H.
Published: May 2010

This article outlines the role of bladder cancer tumor markers in diagnosis and therapy with a particular focus on the most important biomarkers. A MEDLINE based literature search was performed to examine the field of bladder cancer markers. Further determination of recurrence and progression markers will contribute to establish better treatments for the individual patient. Molecular staging of urological tumors will allow selecting cases that will require systemic treatment. Therapeutically, knowledge of cancer progression pathways allow for drug therapies against specific tumor targets. It is necessary and important to integrate under the same objectives basic translational and clinical research.