bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence of “
Candidatus
Liberibacter asiaticus” from California
Authors: Zheng Z. , Deng X. , Chen J. 
Published: October 2014

ABSTRACT

We report here the draft genome sequence of “
Candidatus
Liberibacter asiaticus” strain HHCA, collected from a lemon tree in California. The HHCA strain has a genome size of 1,150,620 bp, 36.5% G+C content, 1,119 predicted open reading frames, and 51 RNA genes.
The Polyamine Catabolic Enzyme SAT1 Modulates Tumorigenesis and Radiation Response in GBM
Authors: Brett-Morris Adina , Wright Bradley M. , Seo Yuji , Pasupuleti Vinay , Zhang Junran , Lu Jun , Spina Raffaella , Bar Eli E. , Gujrati Maneesh , Schur Rebecca , Lu Zheng-Rong , Welford Scott M. 
Published: October 2014

Abstract
Glioblastoma multiforme (GBM) is the most common and severe form of brain cancer. The median survival time of patients is approximately 12 months due to poor responses to surgery and chemoradiation. To understand the mechanisms involved in radioresistance, we conducted a genetic screen using an shRNA library to identify genes in which inhibition would sensitize cells to radiation. The results were cross-referenced with the Oncomine and Rembrandt databases to focus on genes that are highly expressed in GBM tumors and associated with poor patient outcomes. Spermidine/spermine-N1-acetyltransferase 1 (SAT1), an enzyme involved in polyamine catabolism, was identified as a gene that promotes resistance to ionizing radiation (IR), is overexpressed in brain tumors, and correlates with poor outcomes. Knockdown of SAT1 using shRNA and siRNA approaches in multiple cell and neurosphere lines resulted in sensitization of GBM cells to radiation in colony formation assays and tumors, and decreased tumorigenesis in vivo. Radiosensitization occurred specifically in G2–M and S phases, suggesting a role for SAT1 in homologous recombination (HR) that was confirmed in a DR-GFP reporter system. Mechanistically, we found that SAT1 promotes acetylation of histone H3, suggesting a new role of SAT1 in chromatin remodeling and regulation of gene expression. In particular, SAT1 depletion led to a dramatic reduction in BRCA1 expression, explaining decreased HR capacity. Our findings suggest that the biologic significance of elevated SAT1 expression in GBM lies in its contribution to cell radioresistance and that SAT1 may potentially be a therapeutic target to sensitize GBM to cancer therapies. Cancer Res; 74(23); 6925–34. ©2014 AACR.
UGT1A and UGT2B Genetic Variation Alters Nicotine and Nitrosamine Glucuronidation in European and African American Smokers
Authors: Wassenaar Catherine A. , Conti David V. , Das Soma , Chen Peixian , Cook Edwin H. , Ratain Mark J. , Benowitz Neal L. , Tyndale Rachel F. 
Published: October 2014

Abstract
Background: Identifying sources of variation in the nicotine and nitrosamine metabolic inactivation pathways is important to understanding the relationship between smoking and cancer risk. Numerous UGT1A and UGT2B enzymes are implicated in nicotine and nitrosamine metabolism in vitro; however, little is known about their roles in vivo.
Methods: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for nicotine, cotinine, trans-3′-hydroxycotinine, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), was investigated in regression models assuming a dominant effect of variant alleles.
Results: Correcting for multiple testing, three UGT2B10 variants were associated with cotinine glucuronidation, rs2331559 and rs11726322 in European Americans and rs835309 in African Americans (P ≤ 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with nicotine (P = 0.008–0.04) and cotinine (P = &lt;0.001–0.02) glucuronidation in both ethnicities in addition to UGT2B10*2 in European Americans (P = 0.01, P &lt; 0.001). UGT2B17*2 (P = 0.03) in European Americans and UGT2B7 variants (P = 0.02–0.04) in African Americans were nominally associated with 3HC glucuronidation. UGT1A (P = 0.007–0.01), UGT2B10 (P = 0.02), and UGT2B7 (P = 0.02–0.03) variants in African Americans were nominally associated with NNAL glucuronidation.
Conclusions: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of tobacco-related compounds in vivo, in particular UGT2B10 and cotinine glucuronidation.
Impact: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related cancers. Cancer Epidemiol Biomarkers Prev; 24(1); 94–104. ©2014 AACR.
iNOS Expression in CD4+ T Cells Limits Treg Induction by Repressing TGFβ1: Combined iNOS Inhibition and Treg Depletion Unmask Endogenous Antitumor Immunity
Authors: Jayaraman Padmini , Alfarano Matthew G. , Svider Peter F. , Parikh Falguni , Lu Geming , Kidwai Sarah , Xiong Huabao , Sikora Andrew G. 
Published: October 2014

AbstractPurpose: Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4+FOXP3+ regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity.Experimental Design: Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4+ T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA.Results: Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3+ Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4+ T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8+ T-cell levels, and arrested tumor growth in an immune-dependent fashion.Conclusions: iNOS expression in CD4+ T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously. Clin Cancer Res; 20(24); 6439–51. ©2014 AACR.
HPV Infection–Associated Cancers: Next-Generation Technology for Diagnosis and Treatment
Authors: Trimble Cornelia L. 
Published: October 2014

Abstract
Disease caused by human papillomavirus (HPV) remains common, despite preventive vaccines and screening strategies. Globally, HPVs cause one third of infection-associated cancers. The indolent clinical course of the precursor intraepithelial lesions provides an opportunity to understand immunologic obstacles posed by the microenvironment of incipient disease, and how they might be overcome. Results from recent therapeutic HPV vaccine clinical trials suggest that relevant immune responses may be sequestered at the lesion site and are difficult to detect in the circulation. In this Cancer Immunology at the Crossroads article, we outline the current understanding of the risk, diagnosis, and treatment of HPV infection–associated cancers and suggest that quantitative tissue–based endpoints should be included whenever possible in the evaluation of immune-based therapies. Cancer Immunol Res; 2(10); 937–42. ©2014 AACR.
Identification of Small Proline-Rich Repeat Protein 3 as a Novel Atheroprotective Factor That Promotes Adaptive Akt Signaling in Vascular Smooth Muscle Cells
Authors: Segedy Amanda K. , Pyle Amy L. , Li Bin , Zhang Youmin , Babaev Vladimir R. , Jat Parmjit , Fazio Sergio , Atkinson James B. , Linton MacRae F. , Young Pampee P. 
Published: October 2014

Objective—
Atherosclerosis is the primary driver of cardiovascular disease, the leading cause of death worldwide. Identification of naturally occurring atheroprotective genes has become a major goal for the development of interventions that will limit atheroma progression and associated adverse events. To this end, we have identified small proline-rich repeat protein (SPRR3) as selectively upregulated in vascular smooth muscle cells (VSMCs) of atheroma-bearing arterial tissue versus healthy arterial tissue. In this study, we sought to determine the role of SPRR3 in atheroma pathophysiology.

Approach and Results—

We found that atheroprone apolipoprotein E-null mice lacking SPRR3 developed significantly greater atheroma burden. To determine the cellular driver(s) of this increase, we evaluated SPRR3-dependent changes in bone marrow–derived cells, endothelial cells, and VSMCs. Bone marrow transplant of SPRR3-expressing cells into SPRR3
−/−
apolipoprotein E–deficient recipients failed to rescue atheroma burden. Similarly, endothelial cells did not exhibit a response to SPRR3 loss. However, atheromas from SPRR3-deficient mice exhibited increased TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive VSMCs compared with control. Cell death in SPRR3-deficient VSMCs was significantly increased in vitro. Conversely, SPRR3-overexpressing VSMCs exhibited reduced apoptosis compared with control. We also observed a PI3K (phosphatidylinositol 3-kinase)/Akt-dependent positive association between SPRR3 expression and levels of active Akt in VSMCs. The survival advantage seen in SPRR3-overexpressing VSMCs was abrogated after the addition of a PI3K/Akt pathway inhibitor.

Conclusions—
These results indicate that SPRR3 protects the lesion from VSMC loss by promoting survival signaling in plaque VSMCs, thereby significantly decreasing atherosclerosis progression. As the first identified atheroma-specific VSMC prosurvival factor, SPRR3 represents a potential target for lesion-specific modulation of VSMC survival.
PCSK9 R46L, Lower LDL, and Cardiovascular Disease Risk in Familial Hypercholesterolemia
Authors: Luna Saavedra Yascara Grisel , Dufour Robert , Davignon Jean , Baass Alexis 
Published: October 2014

Objective—
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a downregulator of the low density lipoprotein receptor. The aims of this cross-sectional cohort-study were to examine whether the PCSK9 R46L loss of function variant found in a cohort of familial hypercholesterolemia (FH) patients was associated with lower low density lipoprotein cholesterol, lower frequency of xanthomata, and cardiovascular risk.

Approach and Results—

We studied FH patients attending the IRCM (Institut de Recherches Cliniques de Montréal) Lipid Clinic and whose DNA genotyping was positive for a low density lipoprotein receptor mutation. The presence of the PCSK9 loss of function R46L missense variant was determined among a cohort of 582 FH patients by genotyping. Frequency of the R46L variant was 3%. Carriers had significantly lower low density lipoprotein cholesterol (11%,
P
=0.002), total cholesterol (9%,
P
=0.007), apolipoprotein B (10%,
P
=0.037), and non-high density lipoprotein (12%,
P
<0.001) concentrations compared with noncarriers. Furthermore, R46L carriers showed a decreased average number of xanthoma per individual compared with noncarriers (0.33 and 0.76, respectively;
P
<0.001). Importantly, the R46L genetic variant was associated with a significant 86% lower odd of presenting a cardiovascular event (odds ratio, 0.14; 95% confidence interval, 0.032–0.63;
P
=0.001).

Conclusions—
Even though the R46L variant was present in 3% of our FH population, carriers of this polymorphism showed attenuated effect of the low density lipoprotein receptor mutation on parameters, such as low density lipoprotein cholesterol, apolipoprotein B, total cholesterol, and non-high density lipoprotein. More importantly, this mutation is associated with a significant lower risk of cardiovascular disease compared with noncarriers. It is therefore likely that targeting PCSK9 in FH patients with novel anti-PCSK9 therapies will be useful in reducing cardiovascular risk in affected subjects.
Elevation in High-Sensitivity Troponin T in Heart Failure and Preserved Ejection Fraction and Influence of Treatment With the Angiotensin Receptor Neprilysin Inhibitor LCZ696
Authors: Jhund Pardeep S. , Claggett Brian L. , Voors Adriaan A. , Zile Michael R. , Packer Milton , Pieske Burkert M. , Kraigher-Krainer Elisabeth , Shah Amil M. , Prescott Margaret F. , Shi Victor , Lefkowitz Marty , McMurray John J.V. , Solomon Scott D. 
Published: October 2014

Background—
Elevated high-sensitivity troponin is associated with increasing disease severity in patients with stable heart failure with reduced ejection fraction, but less is known about the association in heart failure with preserved ejection fraction.

Methods and Results—

We examined the prevalence of elevated high-sensitivity troponin T (hs-TnT) in 298 patients with heart failure with preserved ejection fraction enrolled in the Prospective comparison of angiotensin receptor neprilysin inhibitor with angiotensin receptor blocker on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial, in which the angiotensin receptor neprilysin inhibitor LCZ696 reduced markers of heart failure severity compared with valsartan. We assessed the association between hs-TnT and cardiac structure and function, and the effect of LCZ696, compared with valsartan, on hs-TnT over 36 weeks. Elevated hs-TnT in the myocardial injury range (>0.014 μg/L) was found in 55% of patients and was associated with older age, history of diabetes mellitus, higher N-terminal pro-brain natriuretic peptide, lower estimated glomerular filtration rate, and larger left atrial size, left ventricular volume, and mass. LCZ696 treatment reduced hs-TnT to a greater extent at 12 weeks (12% reduction;
P
=0.05) and at 36 weeks (14% reduction;
P
=0.03) compared with valsartan.

Conclusions—
Troponin T was elevated in a substantial number of patients enrolled in a heart failure with preserved ejection fraction clinical trial and was associated with abnormalities of cardiac structure, function, and elevated baseline N-terminal pro-brain natriuretic peptide. Decreases in hs-TnT with LCZ696 in parallel with improvement in N-terminal pro-brain natriuretic peptide and left atrial size suggest that the angiotensin receptor neprilysin inhibitor LCZ696 may reduce this measure of myocardial injury in heart failure with preserved ejection fraction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00887588.
Quantitative T2′-Mapping in Acute Ischemic Stroke
Authors: Bauer Sonja , Wagner Marlies , Seiler Alexander , Hattingen Elke , Deichmann Ralf , Nöth Ulrike , Singer Oliver C. 
Published: October 2014

Background and Purpose—
Quantitative T2′-mapping detects regional changes in the relation of oxygenated and deoxygenated haemoglobine and might reflect areas with increased oxygen extraction. T2′-mapping in conjunction with an elaborate algorithm for motion correction was performed in patients with acute large-vessel stroke, and quantitative T2′-values were determined within the diffusion-weighted imaging lesion and perfusion-restricted tissue.

Methods—
Eleven patients (median age, 71 years) with acute middle cerebral or internal carotid artery occlusion underwent MRI before scheduled endovascular treatment. MR-examination included diffusion- and perfusion-weighted imaging and quantitative, motion-corrected mapping of T2′. Time-to-peak maps were thresholded for different degrees of perfusion delays (eg, ≥0 s, ≥ 2s) when compared with a reference time-to-peak value from healthy contralateral tissue. Mean T2′-values in areas with reduced apparent diffusion coefficient and in areas with impaired perfusion were compared with T2′-values in corresponding contralateral areas.

Results—

Median time between symptom onset and MRI was 238 minutes. T2′-values were significantly reduced within the apparent diffusion coefficient -lesion when compared with contralateral healthy tissue (83 ms [67, 97] versus 97 ms [91, 111];
P
<0.003). In perfusion-restricted tissue, T2′-values were also significantly lower when compared with contralateral healthy tissue (ie, for time to peak, ≥0 s 93 ms [86, 102] versus 104 [90, 110];
P
=0.008) but were significantly higher than within the apparent diffusion coefficient lesion. The severity of the perfusion impairment had no influence on median T2′-values.

Conclusions—
Motion-corrected T2′-mapping reveals significant and gradually declining values from healthy to perfusion-disturbed to apparent diffusion coefficient-restricted tissue. Current T2′-mapping can differentiate between the ischemic core and the perfusion-impaired areas but not on its own between penumbral and oligemic tissue.
E-typing for nematodes: an assessment of type specimen use by nematode taxonomists with a summary of types deposited in the Smithsonian Nematode Collection
Authors: Abebe Eyualem , Mekete Tesfamariam , Decraemer Wilfrida 
Published: October 2014

We assessed 301 taxonomic papers published in nine journals between 1999-2011 to determine the use of type specimens and to evaluate the habitat focus and the number of new species described per year. A total of ca 100 new nematode species were described every year, primarily from terrestrial habitats. Two-thirds were terrestrial, 16% were aquatic and the remaining 9% were animal-parasitic nematodes. Only 2.5% of the taxonomic literature reported a comparative study of type material for making a decision on the identity of the target taxon. The overwhelming majority (i.e., 97.5%) relied only on literature comparisons. Our closer scrutiny of the 61 papers revealed a number of shared problems: a third stated that inadequacy of original descriptions, or unavailability/inaccessibility of type specimens had hindered them from unequivocally determining the identity of their species. Fourteen percent reported a discrepancy between the text descriptions and the illustrations, and a tenth revealed the absence of designated types for taxa relevant to their work. A similar number indicated deterioration of types to be a reason for either making wrong conclusions in previous descriptions, or for rendering their descriptions incomplete. We argue for E-typing of nematodes as a solution to enhance the future accessibility of type specimens. We stress the need for a concerted effort between museum curators, nematological journals and nematological societies to address the problem and thereby to forge a brighter future for the science.
<p class="FamilyHeading" align="left">A new species of Lepidium (Brassicaceae) in the Cook Islands
Authors: SYKES W. R. 
Published: October 2014

Lepidium makateanum is a small, erect, densely bushy shrublet confined to areas of makatea (raised coral) on Miti‘aro in the Ngaputoru Group north-east of Rarotonga. It is closely related to L. bidentatum, a common coastal species throughout East Polynesia. On some other islands of East Polynesia, other taxa are also said to be closely related to L. bidentatum, but none represent the Miti‘aro plant.
Moistening Processes before the Convective Initiation of Madden–Julian Oscillation Events during the CINDY2011/DYNAMO Period
Authors: Nasuno Tomoe , Li Tim , Kikuchi Kazuyoshi 
Published: October 2014

Abstract
Convective initiation processes in the Madden–Julian oscillation (MJO) events that occurred during the Cooperative Indian Ocean Experiment on Intraseasonal Variability in the Year 2011 (CINDY2011)/Dynamics of the Madden–Julian Oscillation (DYNAMO) intensive observation period (IOP) were investigated. Two episodes that were initiated in mid-October (MJO1) and mid-November (MJO2) 2011 were analyzed using European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis and satellite data. Moisture budgets in the equatorial Indian Ocean (IO) domain (10°S–10°N, 60°–90°E) were analyzed in detail by separating each variable into basic-state (&gt;80 day), intraseasonal (20–80 day), and high-frequency (&lt;20 day) variations. The quality of the ECMWF reanalysis was also evaluated against the sounding data collected during the field campaign.
In both MJO events, the increase in precipitable water started 8–9 days prior to the convective initiation. Moisture advection decomposition revealed that advection of basic moisture by intraseasonal easterly anomalies and of intraseasonal moisture anomalies by the basic zonal wind were pronounced in these two events. The nonlinear high-frequency terms in the meridional moisture advection were the same order of magnitude as the primary term in the middle troposphere, implying systematic upscale transport of moisture. As a possible mechanism of the acceleration of easterly anomalies, amplification of off-equatorial Rossby wave trains that intruded into the equatorial zone was detected during the preconditioning periods in both MJO events.
Disagreements in Low-Level Moisture between (Re)Analyses over Summertime West Africa
Authors: Roberts Alexander J. , Marsham John H. , Knippertz Peter 
Published: October 2014

Abstract
Reanalysis and operational analysis products are routinely used as the best estimates of the atmospheric state for operational and research purposes. However, different models, assimilation techniques, and assimilated datasets lead to differences between products. Here, such differences in the distribution of low-level water vapor over summertime West Africa are analyzed, as reflected in the zonal mean position of the leading edge of the West African monsoon [the intertropical discontinuity (ITD)] using five reanalyses [NCEP–NCAR, NCEP–Department of Energy (DOE), the Modern-Era Retrospective Analysis for Research and Applications (MERRA), the Climate Forecast System Reanalysis (CFSR), and the Interim ECMWF Re-Analysis (ERA-Interim)] and two operational analyses [Global Forecast System (GFS) and ECMWF] during the 11 monsoon seasons (April–September) from 2000 to 2010. Specific humidity differences regularly reach 50% of the mean value over areas spanning hundreds of kilometers and often coincide with northward excursions of the ITD that last several days and bring unusual rainfall to the Sahel and Sahara. The largest disagreements occur during the southward retreat of the ITD and are connected with anomalously high values of aerosol optical depth, consistent with the production of haboob dust storms. The results suggest that known errors in the representation of moist convection and cold pools may contribute to the identified disagreements. A large reduction in disagreement occurs in 2006, when upper-air observations were enhanced during the African Monsoon Multidisciplinary Analysis (AMMA) campaign, pointing to an insufficient observational constraint of the (re)analyses in other years. It is hoped that this work will raise awareness of the limited reliability of (re)analysis products over West Africa during the summer, particularly during northward surges of the ITD, and will instigate further work to improve their quality.