bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homologs of the Acinetobacter baumannii AceI Transporter Represent a New Family of Bacterial Multidrug Efflux Systems
Authors: Hassan Karl A. , Liu Qi , Henderson Peter J. F. , Paulsen Ian T. 
Published: February 2015

ABSTRACT

Multidrug efflux systems are a major cause of resistance to antimicrobials in bacteria, including those pathogenic to humans, animals, and plants. These proteins are ubiquitous in these pathogens, and five families of bacterial multidrug efflux systems have been identified to date. By using transcriptomic and biochemical analyses, we recently identified the novel AceI (
Acinetobacter
chlorhexidine efflux) protein from
Acinetobacter baumannii
that conferred resistance to the biocide chlorhexidine, via an active efflux mechanism. Proteins homologous to AceI are encoded in the genomes of many other bacterial species and are particularly prominent within proteobacterial lineages. In this study, we expressed 23 homologs of AceI and examined their resistance and/or transport profiles. MIC analyses demonstrated that, like AceI, many of the homologs conferred resistance to chlorhexidine. Many of the AceI homologs conferred resistance to additional biocides, including benzalkonium, dequalinium, proflavine, and acriflavine. We conducted fluorimetric transport assays using the AceI homolog from
Vibrio parahaemolyticus
and confirmed that resistance to both proflavine and acriflavine was mediated by an active efflux mechanism. These results show that this group of AceI homologs represent a new family of bacterial multidrug efflux pumps, which we have designated the proteobacterial antimicrobial compound efflux (PACE) family of transport proteins.

IMPORTANCE
Bacterial multidrug efflux pumps are an important class of resistance determinants that can be found in every bacterial genome sequenced to date. These transport proteins have important protective functions for the bacterial cell but are a significant problem in the clinical setting, since a single efflux system can mediate resistance to many structurally and mechanistically diverse antibiotics and biocides. In this study, we demonstrate that proteins related to the
Acinetobacter baumannii
AceI transporter are a new class of multidrug efflux systems which are very common in
Proteobacteria
: the proteobacterial antimicrobial compound efflux (PACE) family. This is the first new family of multidrug efflux pumps to be described in 15 years.
Subcellular Investigation of Photosynthesis-Driven Carbon Assimilation in the Symbiotic Reef Coral
Pocillopora damicornis
Authors: Kopp Christophe , Domart-Coulon Isabelle , Escrig Stephane , Humbel Bruno M. , Hignette Michel , Meibom Anders 
Published: February 2015

ABSTRACT

Reef-building corals form essential, mutualistic endosymbiotic associations with photosynthetic
Symbiodinium
dinoflagellates, providing their animal host partner with photosynthetically derived nutrients that allow the coral to thrive in oligotrophic waters. However, little is known about the dynamics of these nutritional interactions at the (sub)cellular level. Here, we visualize with submicrometer spatial resolution the carbon and nitrogen fluxes in the intact coral-dinoflagellate association from the reef coral
Pocillopora damicornis
by combining nanoscale secondary ion mass spectrometry (NanoSIMS) and transmission electron microscopy with pulse-chase isotopic labeling using [
13
C]bicarbonate and [
15
N]nitrate. This allows us to observe that (i) through light-driven photosynthesis, dinoflagellates rapidly assimilate inorganic bicarbonate and nitrate, temporarily storing carbon within lipid droplets and starch granules for remobilization in nighttime, along with carbon and nitrogen incorporation into other subcellular compartments for dinoflagellate growth and maintenance, (ii) carbon-containing photosynthates are translocated to all four coral tissue layers, where they accumulate after only 15 min in coral lipid droplets from the oral gastroderm and within 6 h in glycogen granules from the oral epiderm, and (iii) the translocation of nitrogen-containing photosynthates is delayed by 3 h.

IMPORTANCE
Our results provide detailed
in situ
subcellular visualization of the fate of photosynthesis-derived carbon and nitrogen in the coral-dinoflagellate endosymbiosis. We directly demonstrate that lipid droplets and glycogen granules in the coral tissue are sinks for translocated carbon photosynthates by dinoflagellates and confirm their key role in the trophic interactions within the coral-dinoflagellate association.
Neisseria gonorrhoeae Elicits Extracellular Traps in Primary Neutrophil Culture While Suppressing the Oxidative Burst
Authors: Gunderson Carl W. , Seifert H. Steven 
Published: February 2015

ABSTRACT

Neisseria gonorrhoeae
(the gonococcus) causes gonorrhea and is uniquely adapted to survive within the human reproductive tract. Gonococci evade host immune surveillance in part by varying their pili and opacity-associated proteins. These variable surface antigens influence interactions with host epithelial and immune cells. A potent polymorphonuclear leukocyte (PMN) response is a hallmark of symptomatic gonococcal infection, with vast numbers of PMNs recruited to the site of infection. A large body of literature describes gonococcus-PMN interactions, but the factors driving the outcome of infection are not fully understood. Gonococci have been described to both induce and suppress the PMN oxidative burst, but we determined that gonococci differentially affect induction of the PMN oxidative burst depending on the multiplicity of infection (MOI). Infecting PMN at an MOI of <20 gonococci elicits an oxidative burst, while an MOI of >20 suppresses the burst. Oxidative burst in response to gonococci is enhanced by, but does not require, expression of pili or opacity proteins. Neutrophil extracellular traps (NETs) were observed in gonococcus-infected PMNs, a process which requires an oxidative burst, yet gonococci induced NETs under suppressing conditions. The NETs were unable to kill gonococci despite killing the common vaginal bacterium
Lactobacillus crispatus
. Thus, gonococci influence PMN biology to promote their own survival by suppressing the oxidative burst of PMNs and stimulating the formation of NETs, which do not effectively kill gonococci, illustrating how N. gonorrhoeae has evolved to modulate PMN responses to promote infection.

IMPORTANCE

Neisseria gonorrhoeae
, the gonococcus, is the only causative agent of gonorrhea and is exclusively found within the human host. Gonococci stochastically vary the composition of antigens on their surface to evade immune surveillance. We used gonococcal mutants which stably express different surface antigens to dissect interactions between gonococci and primary human polymorphonuclear leukocytes (PMNs). We found that gonococci, depending on the number of bacteria present, either induce or suppress the oxidative burst of PMNs regardless of other stimuli. Gonococci also cause PMNs to release DNA, forming neutrophil extracellular traps (NETs) independently of the oxidative burst. The NETs were unable to kill gonococci but were able to kill commensal bacteria, suggesting that NET production can help gonococci outcompete other bacterial species. We propose that gonococci have evolved to manipulate PMN responses to promote their own survival during infection.
Change in paternity, risk of placental abruption and confounding by birth interval: a population-based prospective cohort study in Norway, 1967–2009
Authors: Ananth Cande V , Skjaerven Rolv , Klunssoyr Kari 
Published: February 2015

ObjectivesWe examined abruption risk in relation to change in paternity, and evaluated if birth interval confounds this association.SettingPopulation-based study of singleton births in Norway between 1967 and 2009.ParticipantsWomen who had their first two (n=747 566) singleton births in the Norwegian Medical Birth Registry. The associations between partner change between pregnancies and birth interval were examined in relation to abruption in a series of logistic regression models.Primary outcome measuresRisk, as well as unadjusted and adjusted OR of placental abruption in relation to change in paternity and interval between births.ResultsAmong women without abruption in their first pregnancy, the risks of abruption in the second pregnancy were 4.7 and 6.5 per 1000 in women who had the same and different partners, respectively (OR=1.39, 95% CI 1.26 to 1.53). After adjustments for confounders including birth interval and smoking, partner change was not associated with abruption (OR=1.01, 95% CI 0.79 to 1.32). Among women with abruption in the first pregnancy, the association between partner change and abruption in the second pregnancy was 0.98 (95% CI 0.75 to 1.28). Interval <1 year was associated with increased abruption risk in the second pregnancy among women with the same as well as different partners, but interval over 4 years was only associated with increased risk among women with the same partner. No such patterns were seen for recurrent abruption.ConclusionsWe find no evidence that a change in partner is associated with increased abruption risk. Theories supporting an immune maladaptation hypothesis afforded by change in paternity are not supported insofar as abruption is concerned.
Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer
Authors: Milagre Carla S. , Gopinathan Ganga , Everitt Gemma , Thompson Richard G. , Kulbe Hagen , Zhong Haihong , Hollingsworth Robert E. , Grose Richard , Bowtell David D.L. , Hochhauser Daniel , Balkwill Frances R. 
Published: February 2015

Abstract
Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer. Cancer Res; 75(7); 1255–64. ©2015 AACR.
Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells
Authors: Cojoc Monica , Peitzsch Claudia , Kurth Ina , Trautmann Franziska , Kunz-Schughart Leoni A. , Telegeev Gennady D. , Stakhovsky Eduard A. , Walker John R. , Simin Karl , Lyle Stephen , Fuessel Susanne , Erdmann Kati , Wirth Manfred P. , Krause Mechthild , Baumann Michael , Dubrovska Anna 
Published: February 2015

Abstract
Radiotherapy is a curative treatment option in prostate cancer. Nevertheless, patients with high-risk prostate cancer are prone to relapse. Identification of the predictive biomarkers and molecular mechanisms of radioresistance bears promise to improve cancer therapies. In this study, we show that aldehyde dehydrogenase (ALDH) activity is indicative of radioresistant prostate progenitor cells with an enhanced DNA repair capacity and activation of epithelial–mesenchymal transition (EMT). Gene expression profiling of prostate cancer cells, their radioresistant derivatives, ALDH+ and ALDH− cell populations revealed the mechanisms, which link tumor progenitors to radioresistance, including activation of the WNT/β-catenin signaling pathway. We found that expression of the ALDH1A1 gene is regulated by the WNT signaling pathway and co-occurs with expression of β-catenin in prostate tumor specimens. Inhibition of the WNT pathway led to a decrease in ALDH+ tumor progenitor population and to radiosensitization of cancer cells. Taken together, our results indicate that ALDH+ cells contribute to tumor radioresistance and their molecular targeting may enhance the effectiveness of radiotherapy. Cancer Res; 75(7); 1482–94. ©2015 AACR.
Phosphotyrosine Signaling Analysis in Human Tumors Is Confounded by Systemic Ischemia-Driven Artifacts and Intra-Specimen Heterogeneity
Authors: Gajadhar Aaron S. , Johnson Hannah , Slebos Robbert J.C. , Shaddox Kent , Wiles Kerry , Washington Mary Kay , Herline Alan J. , Levine Douglas A. , Liebler Daniel C. , White Forest M. 
Published: February 2015

Abstract
Tumor protein phosphorylation analysis may provide insight into intracellular signaling networks underlying tumor behavior, revealing diagnostic, prognostic or therapeutic information. Human tumors collected by The Cancer Genome Atlas program potentially offer the opportunity to characterize activated networks driving tumor progression, in parallel with the genetic and transcriptional landscape already documented for these tumors. However, a critical question is whether cellular signaling networks can be reliably analyzed in surgical specimens, where freezing delays and spatial sampling disparities may potentially obscure physiologic signaling. To quantify the extent of these effects, we analyzed the stability of phosphotyrosine (pTyr) sites in ovarian and colon tumors collected under conditions of controlled ischemia and in the context of defined intratumoral sampling. Cold-ischemia produced a rapid, unpredictable, and widespread impact on tumor pTyr networks within 5 minutes of resection, altering up to 50% of pTyr sites by more than 2-fold. Effects on adhesion and migration, inflammatory response, proliferation, and stress response pathways were recapitulated in both ovarian and colon tumors. In addition, sampling of spatially distinct colon tumor biopsies revealed pTyr differences as dramatic as those associated with ischemic times, despite uniform protein expression profiles. Moreover, intratumoral spatial heterogeneity and pTyr dynamic response to ischemia varied dramatically between tumors collected from different patients. Overall, these findings reveal unforeseen phosphorylation complexity, thereby increasing the difficulty of extracting physiologically relevant pTyr signaling networks from archived tissue specimens. In light of this data, prospective tumor pTyr analysis will require appropriate sampling and collection protocols to preserve in vivo signaling features. Cancer Res; 75(7); 1495–503. ©2015 AACR.
In Vivo Tomographic Imaging of Deep-Seated Cancer Using Fluorescence Lifetime Contrast
Authors: Rice William L. , Shcherbakova Daria M. , Verkhusha Vladislav V. , Kumar Anand T.N. 
Published: February 2015

Abstract
Preclinical cancer research would benefit from noninvasive imaging methods that allow tracking and visualization of early-stage metastasis in vivo. Although fluorescent proteins revolutionized intravital microscopy, two major challenges that still remain are tissue autofluorescence and hemoglobin absorption, which act to limit intravital optical techniques to large or subcutaneous tumors. Here, we use time-domain (TD) technology for the effective separation of tissue autofluorescence from extrinsic fluorophores, based on their distinct fluorescence lifetimes. In addition, we use cancer cells labeled with near infrared fluorescent proteins (iRFP) to allow deep-tissue imaging. Our results demonstrate that TD imaging allows the detection of metastasis in deep-seated organs of living mice with a more than 20-fold increase in sensitivity compared with conventional continuous wave techniques. Furthermore, the distinct fluorescence lifetimes of iRFPs enable lifetime multiplexing of three different tumors, each expressing unique iRFP labels in the same animal. Fluorescence tomographic reconstructions reveal three-dimensional distributions of iRFP720-expressing cancer cells in lungs and brain of live mice, allowing ready longitudinal monitoring of cancer cell fate with greater sensitivity than otherwise currently possible. Cancer Res; 75(7); 1236–43. ©2015 AACR.
History of Allergy and Atopic Dermatitis in Relation to Squamous Cell and Basal Cell Carcinoma of the Skin
Authors: Cheng Judy , Zens M. Scot , Duell Eric , Perry Ann E. , Chapman M. Shane , Karagas Margaret R. 
Published: February 2015

AbstractBackground: Little is known about whether history of allergies and atopy is related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC).Methods: As part of a population-based case–control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). ORs of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors.Results: An overall inverse association was observed between a history of allergy and early onset BCC [OR, 0.61; 95% confidence interval (CI), 0.38–0.97] but not SCC (OR, 1.18; 95% CI, 0.78–1.79). Among women, we found reduced ORs of both early onset BCC and of SCC in relation to allergy history (early onset BCC OR, 0.53; 95% CI, 0.31–0.92 and SCC OR, 0.59; 95% CI, 0.29–1.19). Among men, we observed no clear association with early onset BCC (OR, 0.87; 95% CI, 0.39–1.99) and an increased risk of SCC (OR, 1.58; 95% CI, 0.93–2.69).Conclusion: Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific.Impact: A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancers. Cancer Epidemiol Biomarkers Prev; 24(4); 749–54. ©2015 AACR.
Can fruiting plants control animal behaviour and seed dispersal distance?
Authors: Beaune David , Bretagnolle François , Bollache Loïc , Hohmann Gottfried , Fruth Barbara 
Published: February 2015

In an Afrotropical forest, we tested the hypothesis that fleshy-fruit plants with interspecific differences in fruit quality and quantity affect ranging behaviour of their seed dispersal vector. If fruiting plants could affect their dispersal vector, the plants also affect their seed dispersal distance and eventually their plant population biology. From 2007 to 2011, we measured seed transport by georeference daily bonobo group movements via GPS. Seed dispersal distance was estimated with mechanistic model, using 1200 georeferenced dispersal events and the average seed transit time through bonobo (24.00 h). We compared dissemination for eight plant species that deal with this trade-off: attracting dispersers by means of fruit quality/quantity versus retaining them in the patch because of the same quality/quantity value that attracted them. Because fruit traits of these eight species were different, we expected a difference in seed dispersal distance. Surprisingly, seed dispersal distances induced by bonobos were not affected by fruit traits. Although fruit nutrient contents, abundance and average patch feeding duration differed between plant species, patch feeding time was not related to subsequent dispersal distances. The apes’ dispersal distance survey gave an average dispersal distance estimated of 1332 ± 24 m from the parent plant (97.9% > 100 m). To conclude, feeding time invested in the patch, fruit quality and abundance had no apparent effect on bonobo seed dispersal distance. The possible effects in plant population biology are discussed.
Moving bonobos off the scientifically endangered list
Authors: Hare Brian , Yamamoto Shinya 
Published: February 2015

This Special Issue of Behaviour includes twelve novel empirical papers focusing on the behaviour and cognition of both captive and wild bonobos (Pan paniscus). As our species less known closest relative, the bonobo has gone from being little studied to increasingly popular as a species of focus over the past decade. We suggest that bonobos are ready to come off the scientific endangered list as a result. This Special Issue is exhibit A in showing that a renaissance in bonobo research is well underway. In this Editorial we review a number of traits in which bonobos and chimpanzees are more similar to humans than they are each other. We show how this means that bonobos provide an extremely powerful test of ideas about human uniqueness as well as being crucial to determining the evolutionary processes by which cognitive traits evolve in apes. This introduction places the twelve empirical contributions within the Special Issue in the larger evolutionary context to which they contribute. Overall this Special Issue demonstrates how anyone interested in understanding humans or chimpanzees must also know bonobos.
Mental Disorders and Decision-Making Capacity: What Is the Role of Law?
Authors: Rommelaere Claire 
Published: February 2015

Abstract
When a patient appears to have a mental disorder, doubts may arise about his or her decision-making capacity. Health professionals must then assess the patient’s capacity in order to make sure of the validity of his or her consent or refusal. Incapacity has indeed legal consequences, as law provides for the appointment of a surrogate decision-maker in case of incapacity. With Belgian law as a point of departure, this contribution is aiming at identifying the role of law in capacity assessment itself, prior to the decision about (in)capacity. In order to protect the patient’s rights and to support the task of those carrying out the assessment, law should provide for a global definition of decision-making capacity and for a frame-procedure guiding this assessment. In my opinion, it is possible for law to contribute to the complex task of capacity assessment without interfering embarrassingly with healthcare practice.
Two new freshwater eutardigrade species from Sicily
Authors: PILATO GIOVANNI , SABELLA GIORGIO , LISI OSCAR 
Published: February 2015

Two new species of freshwater Eutardigrada are described from Sicily: Isohypsibius rusticus sp. nov. and Isohypsibius zappalai sp. nov. The former species has eye spots, ornamented body surface with many, variously sized tubercles; bucco-pharyngeal apparatus of the Isohypsibius type; pharyngeal bulb with apophyses and two rod-shaped macroplacoids; microplacoid absent; claws, of the Isohypsibius type, well developed, with long and thin common basal portion; main branches of all claws without free accessory points; very thin lunules present; cuticular bars on the legs absent. Isohypsibius zappalai sp. nov. has eye spots; entire body surface with small tubercles rounded in shape, fairly uniformly sized and tending to form transverse lines; bucco-pharyngeal apparatus of the Isohypsibius type, pharyngeal bulb with apophyses and two macroplacoids; microplacoid absent; claws of the Isohypsibius type, well developed, with long common basal portion and both main and secondary branches with a wide proximal portion. Main branches of all claws with accessory points; small, flexible lunules present; cuticular bars on the legs absent.