bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Coffee Plant-Infecting Xylella fastidiosa Variants Derived via Homologous Recombination
Authors: Jacques Marie-Agnès , Denancé Nicolas , Legendre Bruno , Morel Emmanuelle , Briand Martial , Mississipi Stelly , Durand Karine , Olivier Valérie , Portier Perrine , Poliakoff Françoise , Crouzillat Dominique 
Published: December 2015

ABSTRACT

Xylella fastidiosa
is a xylem-limited phytopathogenic bacterium endemic to the Americas that has recently emerged in Asia and Europe. Although this bacterium is classified as a quarantine organism in the European Union, importation of plant material from contaminated areas and latent infection in asymptomatic plants have engendered its inevitable introduction. In 2012, four coffee plants (
Coffea arabica
and
Coffea canephora
) with leaf scorch symptoms growing in a confined greenhouse were detected and intercepted in France. After identification of the causal agent, this outbreak was eradicated. Three
X. fastidiosa
strains were isolated from these plants, confirming a preliminary identification based on immunology. The strains were characterized by multiplex PCR and by multilocus sequence analysis/typing (MLSA-MLST) based on seven housekeeping genes. One strain, CFBP 8073, isolated from
C. canephora
imported from Mexico, was assigned to
X. fastidiosa
subsp.
fastidiosa/X. fastidiosa
subsp.
sandyi
. This strain harbors a novel sequence type (ST) with novel alleles at two loci. The two other strains, CFBP 8072 and CFBP 8074, isolated from
Coffea arabica
imported from Ecuador, were allocated to
X. fastidiosa
subsp.
pauca
. These two strains shared a novel ST with novel alleles at two loci. These MLST profiles showed evidence of recombination events. We provide genome sequences for CFBP 8072 and CFBP 8073 strains. Comparative genomic analyses of these two genome sequences with publicly available
X. fastidiosa
genomes, including the Italian strain CoDiRO, confirmed these phylogenetic positions and provided candidate alleles for coffee plant adaptation. This study demonstrates the global diversity of
X. fastidiosa
and highlights the diversity of strains isolated from coffee plants.
Important Metabolic Pathways and Biological Processes Expressed by Chicken Cecal Microbiota
Authors: Polansky Ondrej , Sekelova Zuzana , Faldynova Marcela , Sebkova Alena , Sisak Frantisek , Rychlik Ivan 
Published: December 2015

ABSTRACT

The gut microbiota plays important roles in its host. However, how each microbiota member contributes to the behavior of the whole population is not known. In this study, we therefore determined protein expression in the cecal microbiota in chickens of selected ages and in 7-day-old chickens inoculated with different cecal extracts on the day of hatching.
Campylobacter
,
Helicobacter
,
Mucispirillum
, and
Megamonas
overgrew in the ceca of 7-day-old chickens inoculated with cecal extracts from donor hens.
Firmicutes
were characterized by ABC and phosphotransferase system (PTS) transporters, extensive acyl coenzyme A (acyl-CoA) metabolism, and expression of
l
-fucose isomerase.
Anaerostipes
,
Anaerotruncus
,
Pseudoflavonifractor
,
Dorea
,
Blautia
, and
Subdoligranulum
expressed spore proteins.
Firmicutes
(
Faecalibacterium
,
Butyrivibrio
,
Megasphaera
,
Subdoligranulum
,
Oscillibacter
,
Anaerostipes
, and
Anaerotruncus
) expressed enzymes required for butyrate production.
Megamonas
,
Phascolarctobacterium
, and
Blautia
(exceptions from the phylum
Firmicutes
) and all
Bacteroidetes
expressed enzymes for propionate production pathways. Representatives of
Bacteroidetes
also expressed xylose isomerase, enzymes required for polysaccharide degradation, and ExbBD, TonB, and outer membrane receptors likely to be involved in oligosaccharide transport. Based on our data,
Anaerostipes
,
Anaerotruncus
, and
Subdoligranulum
might be optimal probiotic strains, since these represent spore-forming butyrate producers. However, certain care should be taken during microbiota transplantation because the microbiota may behave differently in the intestinal tract of a recipient depending on how well the existing communities are established.
Phosphoenolpyruvate Phosphotransferase System Components Modulate Gene Transcription and Virulence of Borrelia burgdorferi
Authors: Khajanchi Bijay K. , Odeh Evelyn , Gao Lihui , Jacobs Mary B. , Philipp Mario T. , Lin Tao , Norris Steven J. 
Published: December 2015

ABSTRACT

The phosphoenolpyruvate phosphotransferase system (PEP-PTS) and adenylate cyclase (AC) IV (encoded by BB0723 [
cyaB
]) are well conserved in different species of
Borrelia
. However, the functional roles of PEP-PTS and AC in the infectious cycle of
Borrelia
have not been characterized previously. We examined 12 PEP-PTS transporter component mutants by needle inoculation of mice to assess their ability to cause mouse infection. Transposon mutants with mutations in the EIIBC components (
ptsG
) (BB0645, thought to be involved in glucose-specific transport) were unable to cause infection in mice, while all other tested PEP-PTS mutants retained infectivity. Infectivity was partially restored in an in
trans
-complemented strain of the
ptsG
mutant. While the
ptsG
mutant survived normally in unfed as well as fed ticks, it was unable to cause infection in mice by tick transmission, suggesting that the function of
ptsG
is essential to establish infection by either needle inoculation or tick transmission. In Gram-negative organisms, the regulatory effects of the PEP-PTS are mediated by adenylate cyclase and cyclic AMP (cAMP) levels. A recombinant protein encoded by
B. burgdorferi
BB0723 (a putative
cyaB
homolog) was shown to have adenylate cyclase activity
in vitro
; however, mutants with mutations in this gene were fully infectious in the tick-mouse infection cycle, indicating that its function is not required in this process. By transcriptome analysis, we demonstrated that the
ptsG
gene may directly or indirectly modulate gene expression of
Borrelia burgdorferi
. Overall, the PEP-PTS glucose transporter PtsG appears to play important roles in the pathogenesis of
B. burgdorferi
that extend beyond its transport functions.
Discrete Responses to Limitation for Iron and Manganese in Agrobacterium tumefaciens: Influence on Attachment and Biofilm Formation
Authors: Heindl Jason E. , Hibbing Michael E. , Xu Jing , Natarajan Ramya , Buechlein Aaron M. , Fuqua Clay 
Published: December 2015

ABSTRACT

Transition metals such as iron and manganese are crucial trace nutrients for the growth of most bacteria, functioning as catalytic cofactors for many essential enzymes. Dedicated uptake and regulatory systems have evolved to ensure their acquisition for growth, while preventing toxicity. Transcriptomic analysis of the iron- and manganese-responsive regulons of
Agrobacterium tumefaciens
revealed that there are discrete regulatory networks that respond to changes in iron and manganese levels. Complementing earlier studies, the iron-responsive gene network is quite large and includes many aspects of iron-dependent metabolism and the iron-sparing response. In contrast, the manganese-responsive network is restricted to a limited number of genes, many of which can be linked to transport and utilization of the transition metal. Several of the target genes predicted to drive manganese uptake are required for growth under manganese-limited conditions, and an
A. tumefaciens
mutant with a manganese transport deficiency is attenuated for plant virulence. Iron and manganese limitation independently inhibit biofilm formation by
A. tumefaciens
, and several candidate genes that could impact biofilm formation were identified in each regulon. The biofilm-inhibitory effects of iron and manganese do not rely on recognized metal-responsive transcriptional regulators, suggesting alternate mechanisms influencing biofilm formation. However, under low-manganese conditions the
dcpA
operon is upregulated, encoding a system that controls levels of the cyclic di-GMP second messenger. Mutation of this regulatory pathway dampens the effect of manganese limitation.

IMPORTANCE
Responses to changes in transition metal levels, such as those of manganese and iron, are important for normal metabolism and growth in bacteria. Our study used global gene expression profiling to understand the response of the plant pathogen
Agrobacterium tumefaciens
to changes of transition metal availability. Among the properties that are affected by both iron and manganese levels are those required for normal surface attachment and biofilm formation, but the requirement for each of these transition metals is mechanistically independent from the other.
CD126 and Targeted Therapy with Tocilizumab in Chronic Lymphocytic Leukemia
Authors: Liu Feng-Ting , Jia Li , Wang Ping , Farren Timothy , Li Hong , Hao Xishan , Agrawal Samir G. 
Published: December 2015

Abstract
Purpose: IL6 promotes tumor growth and signal transduction via both its membrane-bound (CD126) and soluble receptors (sCD126). We aimed to study whether the levels of CD126 expression in chronic lymphocytic leukemic (CLL) cells can predict in vitro and in vivo treatment response.
Experimental Design: The levels of membrane-bound CD126 expression were determined on freshly isolated CLL B cells (n = 58) using flow cytometry. These CLL cells were treated with chlorambucil or fludarabine with or without anti-CD126 antibody tocilizumab for 24 hours and IL6-mediated STAT3 transcriptional activity and cell-cycle alteration were evaluated.
Results: CD126 surface expression was found in all cases and positively correlated with the levels of in vivo constitutive STAT3 activity. The levels of CD126 expression were significantly and positively correlated with the resistance of CLL cells to in vitro treatment with chlorambucil or fludarabine and poor in vivo treatment response of CLL patients. Blocking IL6 signaling with the anti-CD126 antibody, tocilizumab, had profound effects on STAT3-mediated survival and growth signals: decreased Mcl-1 and Bcl-xL, favoring an apoptotic profile; and decreased p27 with increased cyclin E and CDK2 expression, leading to cell-cycle shift from G0–G1. These tocilizumab-mediated changes induced chemosensitization in resistant CLL cells, with the greatest effect seen in cells with higher CD126 expression (P &lt; 0.001).
Conclusions: CLL cells with higher CD126 expression are more resistant to treatment in vivo and in vitro via IL6–CD126–STAT3 axis. Blocking CD126 using tocilizumab sensitizes CLL cells to chemotherapy. Clin Cancer Res; 22(10); 2462–9. ©2015 AACR.
Cotargeting Androgen Receptor Splice Variants and mTOR Signaling Pathway for the Treatment of Castration-Resistant Prostate Cancer
Authors: Kato Minoru , Banuelos Carmen A. , Imamura Yusuke , Leung Jacky K. , Caley Daniel P. , Wang Jun , Mawji Nasrin R. , Sadar Marianne D. 
Published: December 2015

Abstract
Purpose: The PI3K/Akt/mTOR pathway is activated in most castration-resistant prostate cancers (CRPC). Transcriptionally active androgen receptor (AR) plays a role in the majority of CRPCs. Therefore, cotargeting full-length (FL) AR and PI3K/Akt/mTOR signaling has been proposed as a possible, more effective therapeutic approach for CRPC. However, truncated AR-splice variants (AR-V) that are constitutively active and dominant over FL-AR are associated with tumor progression and resistance mechanisms in CRPC. It is currently unknown how blocking the PI3K/Akt/mTOR pathway impacts prostate cancer driven by AR-Vs. Here, we evaluated the efficacy and mechanism of combination therapy to block mTOR activity together with EPI-002, an AR N-terminal domain (NTD) antagonist that blocks the transcriptional activities of FL-AR and AR-Vs in models of CRPC.
Experimental Design: To determine the functional roles of FL-AR, AR-Vs, and PI3K/Akt/mTOR pathways, we employed EPI-002 or enzalutamide and BEZ235 (low dose) or everolimus in human prostate cancer cells that express FL-AR or FL-AR and AR-Vs (LNCaP95). Gene expression and efficacy were examined in vitro and in vivo.
Results: EPI-002 had antitumor activity in enzalutamide-resistant LNCaP95 cells that was associated with decreased expression of AR-V target genes (e.g., UBE2C). Inhibition of mTOR provided additional blockade of UBE2C expression. A combination of EPI-002 and BEZ235 decreased the growth of LNCaP95 cells in vitro and in vivo.
Conclusions: Cotargeting mTOR and AR-NTD to block transcriptional activities of FL-AR and AR-Vs provided maximum antitumor efficacy in PTEN-null, enzalutamide-resistant CRPC. Clin Cancer Res; 22(11); 2744–54. ©2015 AACR.
Systemic Correlates of White Adipose Tissue Inflammation in Early-Stage Breast Cancer
Authors: Iyengar Neil M. , Zhou Xi Kathy , Gucalp Ayca , Morris Patrick G. , Howe Louise R. , Giri Dilip D. , Morrow Monica , Wang Hanhan , Pollak Michael , Jones Lee W. , Hudis Clifford A. , Dannenberg Andrew J. 
Published: December 2015

Abstract
Purpose: Obesity, insulin resistance, and elevated levels of circulating proinflammatory mediators are associated with poorer prognosis in early-stage breast cancer. To investigate whether white adipose tissue (WAT) inflammation represents a potential unifying mechanism, we examined the relationship between breast WAT inflammation and the metabolic syndrome and its prognostic importance.
Experimental Design: WAT inflammation was defined by the presence of dead/dying adipocytes surrounded by macrophages forming crown-like structures (CLS) of the breast. Two independent groups were examined in cross-sectional (cohort 1) and retrospective (cohort 2) studies. Cohort 1 included 100 women undergoing mastectomy for breast cancer risk reduction (n = 10) or treatment (n = 90). Metabolic syndrome–associated circulating factors were compared by CLS-B status. The association between CLS of the breast and the metabolic syndrome was validated in cohort 2, which included 127 women who developed metastatic breast cancer. Distant recurrence-free survival (dRFS) was compared by CLS-B status.
Results: In cohorts 1 and 2, breast WAT inflammation was detected in 52 of 100 (52%) and 52 of 127 (41%) patients, respectively. Patients with breast WAT inflammation had elevated insulin, glucose, leptin, triglycerides, C-reactive protein, and IL6 and lower high-density lipoprotein cholesterol and adiponectin (P &lt; 0.05) in cohort 1. In cohort 2, breast WAT inflammation was associated with hyperlipidemia, hypertension, and diabetes (P &lt; 0.05). Compared with patients without breast WAT inflammation, the adjusted HR for dRFS was 1.83 (95% CI, 1.07–3.13) for patients with inflammation.
Conclusions: WAT inflammation, a clinically occult process, helps to explain the relationship between metabolic syndrome and worse breast cancer prognosis. Clin Cancer Res; 22(9); 2283–9. ©2015 AACR.
Defining the Value of a Comparative Approach to Cancer Drug Development
Authors: LeBlanc Amy K. , Mazcko Christina N. , Khanna Chand 
Published: December 2015

Abstract
Comparative oncology as a tool in drug development requires a deeper examination of the value of the approach and examples of where this approach can satisfy unmet needs. This review seeks to demonstrate types of drug development questions that are best answered by the comparative oncology approach. We believe common perceived risks of the comparative approach relate to uncertainty of how regulatory bodies will prioritize or react to data generated from these unique studies conducted in diseased animals, and how these new data will affect ongoing human clinical trials. We contend that it is reasonable to consider these data as potentially informative and valuable to cancer drug development, but as supplementary to conventional preclinical studies and human clinical trials particularly as they relate to the identification of drug-associated adverse events. Clin Cancer Res; 22(9); 2133–8. ©2015 AACR.
Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm
Authors: Jeter Joanne M. , Curiel-Lewandrowski Clara , Stratton Steven P. , Myrdal Paul B. , Warneke James A. , Einspahr Janine G. , Bartels Hubert G. , Yozwiak Michael , Bermudez Yira , Hu Chengcheng , Bartels Peter , Alberts David S. 
Published: December 2015

Abstract
Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage. Cancer Prev Res; 9(2); 128–34. ©2015 AACR.
See related article by Tsai and Hawk, p. 125
Tropospheric QBO–ENSO Interactions and Differences between the Atlantic and Pacific
Authors: Hansen Felicitas , Matthes Katja , Wahl Sebastian 
Published: December 2015

Abstract
This study investigates the interaction of the quasi-biennial oscillation (QBO) and the El Niño–Southern Oscillation (ENSO) in the troposphere separately for the North Pacific and North Atlantic region. Three 145-yr model simulations with NCAR’s Community Earth System Model Whole Atmosphere Community Climate Model (CESM-WACCM) are analyzed where only natural (no anthropogenic) forcings are considered. These long simulations allow the authors to obtain statistically reliable results from an exceptional large number of cases for each combination of the QBO (westerly and easterly) and ENSO phases (El Niño and La Niña). Two different analysis methods were applied to investigate where nonlinearity might play a role in QBO–ENSO interactions. The analyses reveal that the stratospheric equatorial QBO anomalies extend down to the troposphere over the North Pacific during Northern Hemisphere winter only during La Niña and not during El Niño events. The Aleutian low is deepened during QBO westerly (QBOW) as compared to QBO easterly (QBOE) conditions, and the North Pacific subtropical jet is shifted northward during La Niña. In the North Atlantic, the interaction of QBOW with La Niña conditions (QBOE with El Niño) results in a positive (negative) North Atlantic Oscillation (NAO) pattern. For both regions, nonlinear interactions between the QBO and ENSO might play a role. The results provide the potential to enhance the skill of tropospheric seasonal predictions in the North Atlantic and North Pacific region.
Does Humidity’s Seasonal Cycle Affect the Annual-Mean Tropical Precipitation Response to Sulfate Aerosol Forcing?
Authors: Merlis Timothy M. 
Published: December 2015

Abstract
Sulfate aerosol radiative forcing alters the distribution of tropical precipitation in climate model simulations. The annual-mean tropical precipitation change is typically described as arising from an annual-mean change in the mean atmospheric circulation. However, the seasonality of the climatology of tropical humidity may modulate the annual-mean precipitation response. Here, the role of seasonality of tropical humidity is assessed using reanalysis and idealized atmospheric general circulation model (GCM) simulations perturbed by sulfate aerosol radiative forcing. When coupled to an aquaplanet slab ocean with low thermal inertia, the seasonal cycle in GCM simulations of the “continental” regime is large and the annual-mean precipitation change depends on both the seasonally varying perturbation mean meridional circulation and the seasonally varying climatological specific humidity. When coupled to an aquaplanet slab ocean with a higher thermal inertia, the seasonal cycle in GCM simulations of the “oceanic” regime is smaller and the annual-mean precipitation change can be approximated by considering the perturbation convergence of the water vapor flux of the annual-mean perturbation mean meridional circulation and the annual-mean climatological specific humidity. The results of the aquaplanet simulations taken together with the magnitude of the seasonality of humidity in an atmospheric reanalysis suggest that the simplest forms of energetic arguments for the tropical precipitation response to perturbations in the atmospheric energy budget, which neglect an explicit role for the seasonality of the radiative forcing and the climatological specific humidity, are not quantitatively accurate for Earth’s tropical land regions.
Evolution of the Madden–Julian Oscillation in Two Types of El Niño
Authors: Chen Xiong , Ling Jian , Li Chongyin 
Published: December 2015

Abstract
Evolution characteristics of the Madden–Julian oscillation (MJO) during the eastern Pacific (EP) and central Pacific (CP) types of El Niño have been investigated. MJO activities are strengthened over the western Pacific during the predeveloping and developing phases of EP El Niño, but suppressed during the mature and decaying phases. In contrast, MJO activities do not show a clear relationship with CP El Niño before their occurrence over the western Pacific, but they increase over the central Pacific during the mature and decaying phases of CP El Niño. Lag correlation analyses further confirm that MJO activities over the western Pacific in boreal spring and early summer are closely related to EP El Niño up to 2–11 months later, but not for CP El Niño. EP El Niño tends to weaken the MJO and lead to a much shorter range of its eastward propagation. Anomalous descending motions over the Maritime Continent and western Pacific related to El Niño can suppress convection and moisture flux convergence there and weaken MJO activities over these regions during the mature phase of both types of El Niño. MJO activities over the western Pacific are much weaker in EP El Niño due to the stronger anomalous descending motions. Furthermore, the MJO propagates more continuously and farther eastward during CP El Niño because of robust moisture convergence over the central Pacific, which provides adequate moisture for the development of MJO convection.