bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyketide Synthase Gene Diversity within the Microbiome of the Sponge Arenosclera brasiliensis, Endemic to the Southern Atlantic Ocean
Authors: Trindade-Silva Amaro E. , Rua Cintia P. J. , Andrade Bruno G. N. , Vicente Ana Carolina Paulo , Silva Genivaldo G. Z. , Berlinck Roberto G. S. , Thompson Fabiano L. 
Published: December 2012

ABSTRACTMicrobes associated with marine sponges are considered important producers of bioactive, structurally unique polyketides. The synthesis of such secondary metabolites involves type I polyketide synthases (PKSs), which are enzymes that reach a maximum complexity degree in bacteria. The Haplosclerida spongeArenosclera brasiliensishosts a complex microbiota and is the source of arenosclerins, alkaloids with cytotoxic and antibacterial activity. In the present investigation, we performed high-throughput sequencing of the ketosynthase (KS) amplicon to investigate the diversity of PKS genes present in the metagenome ofA. brasiliensis. Almost 4,000 ketosynthase reads were recovered, with about 90% annotated automatically as bacterial. A total of 235 bacterial KS contigs was rigorously assembled from this sequence pool and submitted to phylogenetic analysis. A great diversity of six type I PKS groups has been consistently detected in our phylogenetic reconstructions, including a novel andA. brasiliensis-exclusive group. Our study is the first to reveal the diversity of type I PKS genes inA. brasiliensisas well as the potential of its microbiome to serve as a source of new polyketides.
Real-Time PCR Assays for Quantification of
qnr
Genes in Environmental Water Samples and Chicken Feces
Authors: Marti Elisabet , Balcázar José Luis 
Published: December 2012

ABSTRACT

Real-time PCR assays were developed for the enumeration of plasmid-mediated quinolone resistance (PMQR) determinants, such as the
qnrA
,
qnrB
, and
qnrS
genes, in different water samples and chicken feces. The results indicate that the developed assays are specific and sensitive for the quantification of
qnr
genes in complex samples.
Upgrading Fungal Gene Expression on Demand: Improved Systems for Doxycycline-Dependent Silencing in Aspergillus fumigatus
Authors: Helmschrott Christoph , Sasse Anna , Samantaray Sweta , Krappmann Sven , Wagener Johannes 
Published: December 2012

ABSTRACT

Conditional gene expression is key for functional studies in any given microorganism. To allow tight regulation in the pathogenic mold
Aspergillus fumigatus
, improved versions of the doxycycline-dependent Tet-On system were generated by replacing functional elements of the precursor module, thereby circumventing the former problem of leakiness due to intramolecular recombination.
Validity of theInternational Classification of Diseases 10th revisioncode for hyperkalaemia in elderly patients at presentation to an emergency department and at hospital admission
Authors: Fleet Jamie L , Shariff Salimah Z , Gandhi Sonja , Weir Matthew A , Jain Arsh K , Garg Amit X 
Published: December 2012

ObjectivesEvaluate the validity of theInternational Classification of Diseases, 10th revision(ICD-10) code for hyperkalaemia (E87.5) in two settings: at presentation to an emergency department and at hospital admission.DesignPopulation-based validation study.Setting12 hospitals in Southwestern Ontario, Canada, from 2003 to 2010.ParticipantsElderly patients with serum potassium values at presentation to an emergency department (n=64 579) and at hospital admission (n=64 497).Primary outcomeSensitivity, specificity, positive-predictive value and negative-predictive value. Serum potassium values in patients with and without a hyperkalaemia code (code positive and code negative, respectively).ResultsThe sensitivity of the best-performing ICD-10 coding algorithm for hyperkalaemia (defined by serum potassium >5.5 mmol/l) was 14.1% (95% CI 12.5% to 15.9%) at presentation to an emergency department and 14.6% (95% CI 13.3% to 16.1%) at hospital admission. Both specificities were greater than 99%. In the two settings, the positive-predictive values were 83.2% (95% CI 78.4% to 87.1%) and 62.0% (95% CI 57.9% to 66.0%), while the negative-predictive values were 97.8% (95% CI 97.6% to 97.9%) and 96.9% (95% CI 96.8% to 97.1%). In patients who were code positive for hyperkalaemia, median (IQR) serum potassium values were 6.1 (5.7 to 6.8) mmol/l at presentation to an emergency department and 6.0 (5.1 to 6.7) mmol/l at hospital admission. For code-negative patients median (IQR) serum potassium values were 4.0 (3.7 to 4.4) mmol/l and 4.1 (3.8 to 4.5) mmol/l in each of the two settings, respectively.ConclusionsPatients with hospital encounters who were ICD-10 E87.5 hyperkalaemia code positive and negative had distinct higher and lower serum potassium values, respectively. However, due to very low sensitivity, the incidence of hyperkalaemia is underestimated.
Differences between acute myocardial infarction and unstable angina: a longitudinal cohort study reporting findings from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA)
Authors: Dudas Kerstin , Björck Lena , Jernberg Tomas , Lappas Georgios , Wallentin Lars , Rosengren Annika 
Published: January 2013

ObjectivesThe aim of this study was to compare risk factors and comorbidities in patients with a first episode of acute coronary syndrome (ACS), being either acute myocardial infarction (AMI) or unstable angina pectoris (UAP).DesignCross-sectional and prospective.SettingThe Swedish population.ParticipantsA total of 145 346 consecutive patients aged 25–105 years included in the Swedish Register of Cardiac Intensive Care Admission (Register of Information and Knowledge about Swedish Heart Intensive Care) and admitted to hospital between 1 January 1996 and 30 June 2009 with a first episode of either AMI or UAP.Primary and secondary outcome measuresType of ACS and 1-year outcome.ResultsCompared with patients with UAP, AMI patients were more likely to be older; men; and former or current smokers; they were also more likely to have had diabetes and peripheral artery disease, but had lower rates of prior heart failure (HF) and fewer cardioprotective medications on admission. Among patients aged <65 years, 1.4% of men and 1.6% of women with UAP died within 1 year in 2003–2006 compared with 4.2% of men and 3.1% of women AMI patients (multiple-adjusted OR 3.54 (99% CI 2.29 to 5.48) in women and 2.65 (99% CI 2.11 to 3.34) in men). Corresponding proportions in patients aged ≥65 years was 7.5% in men and 7.6% in women with UAP and 21.5% in men and 17.8% in women with AMI.ConclusionsIn patients with a first-time ACS episode, male sex, slightly older age, smoking, diabetes and peripheral arterial disease (PAD), but fewer cardioprotective medications, were major determinants for presenting with AMI. Despite increasingly active treatment in AMI and more inclusive diagnostic criteria in recent years, persistently worse prognosis was observed in AMI patients.
Introduction to Special Issue ofCanadian Journal of Earth Sciences: Canadian contributions to planetary geoscience
Authors: Williamson Marie-Claude , Johnson Catherine L. , Sylvester Paul J. 
Published: January 2013

The first Special Issue published by the Canadian Journal of Earth Sciences in the field of planetary sciences consists of a collection of nine papers on astromaterials, planetary geology, and Earth-based analogues. We describe the milestones that led to the development of the planetary geology and geophysics (PG&G) community in Canada over the past 5 years, which culminated in record-breaking attendance at a special session of the 2011 GAC–MAC–SEG–SGA Joint Annual Meeting held in Ottawa. The idea of a Special Issue was met with enthusiasm by delegates from coast to coast. By connecting the fields of earth and planetary sciences, the Canadian Journal of Earth Sciences pioneers a new vision for geoscience that expands the options available to Canadians who wish to publish their research at home.
ALX1 Induces Snail Expression to Promote Epithelial-to-Mesenchymal Transition and Invasion of Ovarian Cancer Cells
Authors: Yuan Hong , Kajiyama Hiroaki , Ito Satoko , Yoshikawa Nobuhisa , Hyodo Toshinori , Asano Eri , Hasegawa Hitoki , Maeda Masao , Shibata Kiyosumi , Hamaguchi Michinari , Kikkawa Fumitaka , Senga Takeshi 
Published: January 2013

AbstractOvarian cancer is a highly invasive and metastatic disease with a poor prognosis if diagnosed at an advanced stage, which is often the case. Recent studies argue that ovarian cancer cells that have undergone epithelial-to-mesenchymal transition (EMT) acquire aggressive malignant properties, but the relevant molecular mechanisms in this setting are not well-understood. Here, we report findings from an siRNA screen that identified the homeobox transcription factor ALX1 as a novel regulator of EMT. RNA interference–mediated attenuation of ALX1 expression restored E-cadherin expression and cell–cell junction formation in ovarian cancer cells, suppressing cell invasion, anchorage-independent growth, and tumor formation. Conversely, enforced expression of ALX1 in ovarian cancer cells or nontumorigenic epithelial cells induced EMT. We found that ALX1 upregulated expression of the key EMT regulator Snail (SNAI1) and that it mediated EMT activation and cell invasion by ALX1. Our results define the ALX1/Snail axis as a novel EMT pathway that mediates cancer invasion. Cancer Res; 73(5); 1581–90. ©2012 AACR.
Evidence for a Role of the PD-1:PD-L1 Pathway in Immune Resistance of HPV-Associated Head and Neck Squamous Cell Carcinoma
Authors: Lyford-Pike Sofia , Peng Shiwen , Young Geoffrey D. , Taube Janis M. , Westra William H. , Akpeng Belinda , Bruno Tullia C. , Richmon Jeremy D. , Wang Hao , Bishop Justin A. , Chen Lieping , Drake Charles G. , Topalian Suzanne L. , Pardoll Drew M. , Pai Sara I. 
Published: January 2013

AbstractHuman papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We show membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor-associated macrophages is geographically localized to sites of lymphocyte fronts, whereas the majority of CD8+ tumor-infiltrating lymphocytes express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for IFN-γ, a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an “immune-privileged” site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC. Cancer Res; 73(6); 1733–41. ©2012 AACR.
Acidity Generated by the Tumor Microenvironment Drives Local Invasion
Authors: Estrella Veronica , Chen Tingan , Lloyd Mark , Wojtkowiak Jonathan , Cornnell Heather H. , Ibrahim-Hashim Arig , Bailey Kate , Balagurunathan Yoganand , Rothberg Jennifer M. , Sloane Bonnie F. , Johnson Joseph , Gatenby Robert A. , Gillies Robert J. 
Published: January 2013

Abstract
The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H+ diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion. In the current work, tumor invasion and peritumoral pH were monitored over time using intravital microscopy. In every case, the peritumoral pH was acidic and heterogeneous and the regions of highest tumor invasion corresponded to areas of lowest pH. Tumor invasion did not occur into regions with normal or near-normal extracellular pH. Immunohistochemical analyses revealed that cells in the invasive edges expressed the glucose transporter-1 and the sodium–hydrogen exchanger-1, both of which were associated with peritumoral acidosis. In support of the functional importance of our findings, oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis. Cancer Res; 73(5); 1524–35. ©2012 AACR.
Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling
Authors: Guo Kun , Ma Qingyong , Li Junhui , Wang Zheng , Shan Tao , Li Wei , Xu Qinhong , Xie Keping 
Published: January 2013

Abstract
Perineural invasion (PNI) is one of the most important causes of local recurrence and poor survival in pancreatic cancer. However, the exact mechanism of PNI is still not clear. In this study, we sought to identify the reciprocal signaling interactions between sympathetic nerves and pancreatic cancer cells and the underlying mechanisms. We used mouse dorsal root ganglia and pancreatic cancer cells cocultured in vitro, cellular and molecular biology, and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine (NE) in PNI progression and pathogenesis. NE promoted PNI of pancreatic cancer cells and increased levels of phosphorylated STAT3 in a concentration-dependent manner. NE-mediated activation of STAT3 was inhibited by blocking β-adrenergic receptors (AR) and by blocking protein kinase A, but not through blocking α-AR. Blocking STAT3 could inhibit NE-induced NGF, MMP2, and MMP9 expression and attenuate the migratory, invasive ability and PNI of pancreatic cancer cells. Furthermore, PNI of pancreatic cancer cells was blocked by treatment with a STAT3 phosphorylation inhibitor in vivo. These studies show that NE plays a critical role in pancreatic cancer PNI development and progression through the β-AR/PKA/STAT3 signaling pathway. Reciprocal signaling interactions between the sympathetic nerves and pancreatic cancer cells critically contribute to pancreatic cancer PNI pathogenesis. Inhibition of the activity of sympathetic nerves or STAT3 may be potential strategies for pancreatic cancer PNI therapy. Mol Cancer Ther; 12(3); 264–73. ©2012 AACR.
Increased Interstitial Protein Because of Impaired Lymph Drainage Does Not Induce Fibrosis and Inflammation in Lymphedema
Authors: Markhus C.E. , Karlsen T.V. , Wagner M. , Svendsen Ø.S. , Tenstad O. , Alitalo K. , Wiig H. 
Published: January 2013

Objective—
The pathophysiology of lymphedema is incompletely understood. We asked how transcapillary fluid balance parameters and lymph flow are affected in a transgenic mouse model of primary lymphedema, which due to an inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling lacks dermal lymphatics, and whether protein accumulation in the interstitium occurring in lymphedema results in inflammation.

Methods and Results—
As estimated using a new optical-imaging technique, we found that this signaling defect resulted in lymph drainage in hind limb skin of K14-VEGFR-3-Ig mice that was 34% of the corresponding value in wild-type. The interstitial fluid pressure and tissue fluid volumes were significantly increased in the areas of visible swelling only, whereas the colloid osmotic pressure in plasma, and thus the colloid osmotic pressure gradient, was reduced compared to wild-type mice. An acute volume load resulted in an exaggerated interstitial fluid pressure response in transgenic mice. There was no accumulation of collagen or lipid in skin, suggesting that chronic edema presented in the K14-VEGFR-3-Ig mouse was not sufficient to induce changes in tissue composition. Proinflammatory cytokines (interleukin-2, interleukin-6, interleukin-12) in subcutaneous interstitial fluid and macrophage infiltration in skin of the paw were lower, whereas the monocyte/macrophage cell fraction in blood and spleen was higher in transgenic compared with wild-type mice.

Conclusion—
Our data suggest that a high interstitial protein concentration and longstanding edema is not sufficient to induce fibrosis and inflammation characteristic for the human condition and may have implications for our understanding of the pathophysiology of this condition.
Pioglitazone Attenuates Valvular Calcification Induced by Hypercholesterolemia
Authors: Chu Yi , Lund Donald D. , Weiss Robert M. , Brooks Robert M. , Doshi Hardik , Hajj Georges P. , Sigmund Curt D. , Heistad Donald D. 
Published: January 2013

Objective—
Development of calcific aortic valve stenosis involves multiple signaling pathways, which may be modulated by peroxisome proliferator-activated receptor-γ). This study tested the hypothesis that pioglitazone (Pio), a ligand for peroxisome proliferator-activated receptor-γ, inhibits calcification of the aortic valve in hypercholesteremic mice.

Methods and Results—

Low density lipoprotein receptor
–/–
/apolipoprotein B
100/100
mice were fed a Western-type diet with or without Pio (20 mg/kg per day) for 6 months. Pio attenuated lipid deposition and calcification in the aortic valve, but not aorta. In the aortic valve, Pio reduced levels of active caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Valve function (echocardiography) was significantly improved by Pio. To determine whether changes in gene expression are associated with differential effects of Pio on aortic valves versus aorta, Reversa mice were fed Western diet with or without Pio for 2 months. Several procalcific genes were increased by Western diet, and the increase was attenuated by Pio, in aortic valve, but not aorta.

Conclusion—
Pio attenuates lipid deposition, calcification, and apoptosis in aortic valves of hypercholesterolemic mice, improves aortic valve function, and exhibits preferential effects on aortic valves versus aorta. We suggest that Pio protects against calcific aortic valve stenosis, and Pio or other peroxisome proliferator-activated receptor-γ ligands may be useful for early intervention to prevent or slow stenosis of aortic valves.
Claudin-5 Controls Intercellular Barriers of Human Dermal Microvascular but Not Human Umbilical Vein Endothelial Cells
Authors: Kluger Martin S. , Clark Paul R. , Tellides George , Gerke Volker , Pober Jordan S. 
Published: January 2013

Objective—
To assess the role claudin-5, an endothelial cell (EC) tight junction protein, plays in establishing basal permeability levels in humans by comparing claudin-5 expression levels in situ and analyzing junctional organization and function in 2 widely used models of cultured ECs, namely human dermal microvascular (HDM)ECs and human umbilical vein (HUV)ECs.

Methods and Results—
By immunofluorescence microscopy, ECs more highly express claudin-5 (but equivalently express vascular endothelial-cadherin) in human dermal capillaries versus postcapillary venules and in umbilical and coronary arteries versus veins, correlating with known segmental differences in tight junction frequencies and permeability barriers. Postconfluent cultured HDMECs express more claudin-5 (but equivalent vascular endothelial-cadherin) and show higher transendothelial electric resistance and lower macromolecular flux than similarly cultured HUVECs. HDMEC junctions are more complex by transmission electron microscopy and show more continuous claudin-5 immunofluorescence than HUVEC junctions. Calcium chelation or dominant negative vascular endothelial-cadherin overexpression decreases transendothelial electric resistance and disrupts junctions in HUVECs, but not in HDMECs. Claudin-5 overexpression in HUVECs fails to increase transendothelial electric resistance or claudin-5 continuity, whereas claudin-5 knockdown in HDMECs, but not in HUVECs, reduces transendothelial electric resistance and increases antibody accessibility to junctional proteins.

Conclusion—
Claudin-5 expression and junctional organization control HDMEC and arteriolar-capillary paracellular barriers, whereas HUVEC and venular junctions use vascular endothelial-cadherin.
Landfalling Tropical Cyclones along the Eastern Pacific Coast between the Sixteenth and Twentieth Centuries
Authors: Pazos Marni , Mendoza Blanca 
Published: January 2013

Abstract
Numerous studies have been conducted to document long-term trends in tropical cyclone (TC) activity. However, the eastern Pacific has not received as much attention as other basins. Here the authors attempt the identification of TC formation in the Mexican eastern Pacific Ocean before 1950. Using bibliographical and historical file consultation, they constructed a catalog of events related to intense storms and possible TCs that made landfall on the Mexican Pacific coasts. Between 1536 and 1948 they found a total of 119 events related to TCs. Then, using the Saffir–Simpson scale and the climatology of the region as the criteria to evaluate each event, they found 85 TCs. Furthermore, they constructed a historical time series of TCs between 1701 and 2010. The spectral analysis showed periodicities of ~2.6, 4, 5, 12, 16, 39, and 105 years that coincide with some large-scale climatic phenomena and also with solar activity. In particular, the ~12-yr cycle is the most persistent periodicity in this study.
Mechanical, thermal and morphological properties of poly(lactic acid)/epoxidized natural rubber blends
Authors: Bijarimi Mohd , Ahmad Sahrim , Rasid Rozaidi 
Published: December 2012

In this work, we report a melt blend of poly(lactic acid)(PLA)/epoxidized natural rubber (ENR) with liquid natural rubber (LNR). The LNR was synthesized by a photochemical degradation technique and used as a compatibilizer in the PLA/rubber binary blending systems. The PLA/ENR/LNR blends were melt-blended in a Haake internal mixer at 180°C and mixing speed of 50 r. min−1 for 15 min. It was found that the addition of LNR compatibilizer has improved the tensile strength and elongation at break for the compositions of the 40PLA/55ENR/5LNR blend system when compared with a noncompatibilized system (40PLA/55ENR/5NR). The elongation at break for the blend with 5% LNR compatibilizer showed a twofold increment compared with the blend without LNR. The increase in tensile strength and elongation at break were associated with the ability of LNR to promote the uniform dispersion between the natural rubber (NR) and PLA phases as observed in the scanning electron microscopic analysis. Moreover, the differential scanning calorimetric results indicated that the 40PLA/55ENR/5LNR showed the highest degree of crystallinity and thus contributed to improve their mechanical properties. Thermogravimetric analysis showed that two degradation transitions for both compatibilized and noncompatibilized blend systems due to higher degradation temperatures of ENR50 and NR parts. Fourier transform infrared spectroscopic analysis revealed that the PLA/ENR/NR and PLA/ENR/LNR blends were not miscible.
Targeting transcription factor SALL4 in acute myeloid leukemia by interrupting its interaction with an epigenetic complex
Authors: Gao Chong , Dimitrov Todor , Yong Kol Jia , Tatetsu Hiro , Jeong Ha-won , Luo Hongbo R. , Bradner James E. , Tenen Daniel G. , Chai Li 
Published: January 2013

Key PointsThe SALL4/NuRD/PTEN pathway is important for acute myeloid leukemogenesis. Targeting AML can be achieved by blocking the interaction between transcription factor SALL4 and the epigenetic NuRD complex.