bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic Insight into Trimethylamine
N
-Oxide Recognition by the Marine Bacterium Ruegeria pomeroyi DSS-3
Authors: Li Chun-Yang , Chen Xiu-Lan , Shao Xuan , Wei Tian-Di , Wang Peng , Xie Bin-Bin , Qin Qi-Long , Zhang Xi-Ying , Su Hai-Nan , Song Xiao-Yan , Shi Mei , Zhou Bai-Cheng , Zhang Yu-Zhong 
Published: August 2015

ABSTRACT

Trimethylamine
N
-oxide (TMAO) is an important nitrogen source for marine bacteria. TMAO can also be metabolized by marine bacteria into volatile methylated amines, the precursors of the greenhouse gas nitrous oxide. However, it was not known how TMAO is recognized and imported by bacteria.
Ruegeria pomeroyi
DSS-3, a marine
Roseobacter
, has an ATP-binding cassette transporter, TmoXWV, specific for TMAO. TmoX is the substrate-binding protein of the TmoXWV transporter. In this study, the substrate specificity of TmoX of
R. pomeroyi
DSS-3 was characterized. We further determined the structure of the TmoX/TMAO complex and studied the TMAO-binding mechanism of TmoX by biochemical, structural, and mutational analyses. A Ca
2+
ion chelated by an extended loop in TmoX was shown to be important for maintaining the stability of TmoX. Molecular dynamics simulations indicate that TmoX can alternate between “open” and “closed” states for binding TMAO. In the substrate-binding pocket, four tryptophan residues interact with the quaternary amine of TMAO by cation-π interactions, and Glu131 forms a hydrogen bond with the polar oxygen atom of TMAO. The π-π stacking interactions between the side chains of Phe and Trp are also essential for TMAO binding. Sequence analysis suggests that the TMAO-binding mechanism of TmoX may have universal significance in marine bacteria, especially in the marine
Roseobacter
clade. This study sheds light on how marine microorganisms utilize TMAO.

IMPORTANCE
Trimethylamine
N
-oxide (TMAO) is an important nitrogen source for marine bacteria. The products of TMAO metabolized by bacteria are part of the precursors of the greenhouse gas nitrous oxide. It is unclear how TMAO is recognized and imported by bacteria. TmoX is the substrate-binding protein of a TMAO-specific transporter. Here, the substrate specificity of TmoX of
Ruegeria pomeroyi
DSS-3 was characterized. The TMAO-binding mechanism of TmoX was studied by biochemical, structural, and mutational analyses. Moreover, our results suggest that the TMAO-binding mechanism may have universal significance in marine bacteria. This study sheds light on how marine microorganisms utilize TMAO and should lead to a better understanding of marine nitrogen cycling.
Posterior circulation CT angiography collaterals predict outcome of endovascular acute ischemic stroke therapy for basilar artery occlusion
Authors: Goyal Nitin , Tsivgoulis Georgios , Nickele Chris , Doss Vinodh T , Hoit Dan , Alexandrov Andrei V , Arthur Adam , Elijovich Lucas 
Published: August 2015

IntroductionThe natural history of acute ischemic stroke (AIS) due to basilar artery occlusion (BAO) is poor. Endovascular reperfusion therapy (EVT) improves recanalization rates in patients with emergent large vessel intracranial occlusion.ObjectiveTo examine the hypothesis that good collateral patterns identified by pretreatment CT angiography (CTA) might be associated with favorable outcomes after EVT.MethodsWe conducted a retrospective chart review of patients presenting with AIS due to BAO in a tertiary care stroke center during a 4-year period. BAO was diagnosed by CTA in all cases. Admission stroke severity was documented using the National Institute of Health Stroke Scale (NIHSS) score. Pretreatment collateral score for posterior circulation was defined as follows: 0, no posterior communicating artery (PCOM); 1, unilateral PCOM; 2, bilateral PCOM. Favorable outcome was defined as modified Rankin Scale score of 0–2 at 3 months.ResultsA total of 21 patients with AIS due to BAO (age range 31–84 years, median admission NIHSS score: 18 points, range 2–38) underwent EVT. Eleven of 21 patients (52.4%) had bilateral PCOMs, while unilateral PCOM was seen in 3 patients (14.3%). Patients with bilateral PCOMs tended (p=0.261) to have less severe stroke at admission than those with absent/unilateral PCOM (median NIHSS score 18 vs 27 points). Neurological improvement during hospitalization (quantified by the median decrease in NIHSS score) and the rate of 3-month functional independence were greater in patients with good collaterals (16 vs 0 points (p=0.016) and 72.7% vs 0% (p=0.001)).ConclusionsThe presence of bilateral PCOMs on pretreatment CTA appears to be associated with more favorable outcomes in BAO treated with EVT.
Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma
Authors: Phan Liem M. , Fuentes-Mattei Enrique , Wu Weixin , Velazquez-Torres Guermarie , Sircar Kanishka , Wood Christopher G. , Hai Tao , Jimenez Camilo , Cote Gilbert J. , Ozsari Levent , Hofmann Marie-Claude , Zheng Siyuan , Verhaak Roeland , Pagliaro Lance , Cortez Maria Angelica , Lee Mong-Hong , Yeung Sai-Ching J. , Habra Mouhammed Amir 
Published: August 2015

Abstract
Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited response to chemotherapy. Hepatocyte growth factor (HGF) and its receptor cMET augment cancer growth and resistance to chemotherapy, but their role in adrenocortical carcinoma has not been examined. In this study, we investigated the association between HGF/cMET expression and cancer hallmarks of adrenocortical carcinoma. Transcriptomic and immunohistochemical analyses indicated that increased HGF/cMET expression in human adrenocortical carcinoma samples was positively associated with cancer-related biologic processes, including proliferation and angiogenesis, and negatively correlated with apoptosis. Accordingly, treatment of adrenocortical carcinoma cells with exogenous HGF resulted in increased cell proliferation in vitro and in vivo while short hairpin RNA–mediated knockdown or pharmacologic inhibition of cMET suppressed cell proliferation and tumor growth. Moreover, exposure of cells to mitotane, cisplatin, or radiation rapidly induced pro-cMET expression and was associated with an enrichment of genes (e.g., CYP450 family) related to therapy resistance, further implicating cMET in the anticancer drug response. Together, these data suggest an important role for HGF/cMET signaling in adrenocortical carcinoma growth and resistance to commonly used treatments. Targeting cMET, alone or in combination with other drugs, could provide a breakthrough in the management of this aggressive cancer. Cancer Res; 75(19); 4131–42. ©2015 AACR.
Transcriptome Sequencing Reveals PCAT5 as a Novel ERG-Regulated Long Noncoding RNA in Prostate Cancer
Authors: Ylipää Antti , Kivinummi Kati , Kohvakka Annika , Annala Matti , Latonen Leena , Scaravilli Mauro , Kartasalo Kimmo , Leppänen Simo-Pekka , Karakurt Serdar , Seppälä Janne , Yli-Harja Olli , Tammela Teuvo L.J. , Zhang Wei , Visakorpi Tapio , Nykter Matti 
Published: August 2015

Abstract
Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking therapies cause most of the deaths from prostate cancer, intensifying the need to fully understand CRPC pathophysiology. In this study, we characterized the transcriptomic differences between untreated prostate cancer and locally recurrent CRPC. Here, we report the identification of 145 previously unannotated intergenic long noncoding RNA transcripts (lncRNA) or isoforms that are associated with prostate cancer or CRPC. Of the one third of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regulatory target for the transcription factor ERG, which is activated in approximately 50% of human prostate cancer. Genome-wide expression analysis of a PCAT5-positive prostate cancer after PCAT5 silencing highlighted alterations in cell proliferation pathways. Strikingly, an in vitro validation of these alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion, colony-forming potential, and apoptosis. Our findings reveal a key molecular determinant of differences between prostate cancer and CRPC at the level of the transcriptome. Furthermore, they establish PCAT5 as a novel oncogenic lncRNA in ERG-positive prostate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions. Cancer Res; 75(19); 4026–31. ©2015 AACR.
Interactions between Ibrutinib and Anti-CD20 Antibodies: Competing Effects on the Outcome of Combination Therapy
Authors: Skarzynski Martin , Niemann Carsten U. , Lee Yuh Shan , Martyr Sabrina , Maric Irina , Salem Dalia , Stetler-Stevenson Maryalice , Marti Gerald E. , Calvo Katherine R. , Yuan Constance , Valdez Janet , Soto Susan , Farooqui Mohammed Z.H. , Herman Sarah E.M. , Wiestner Adrian 
Published: August 2015

Abstract
Purpose: Clinical trials of ibrutinib combined with anti-CD20 monoclonal antibodies (mAb) for chronic lymphocytic leukemia (CLL) report encouraging results. Paradoxically, in preclinical studies, in vitro ibrutinib was reported to decrease CD20 expression and inhibit cellular effector mechanisms. We therefore set out to investigate effects of in vivo ibrutinib treatment that could explain this paradox.
Experimental Design: Patients received single-agent ibrutinib (420 mg daily) on an investigator-initiated phase II trial. Serial blood samples were collected pretreatment and during treatment for ex vivo functional assays to examine the effects on CLL cell susceptibility to anti-CD20 mAbs.
Results: We demonstrate that CD20 expression on ibrutinib was rapidly and persistently downregulated (median reduction 74%, day 28, P &lt; 0.001) compared with baseline. Concomitantly, CD20 mRNA was decreased concurrent with reduced NF-κB signaling. An NF-κB binding site in the promoter of MS4A1 (encoding CD20) and downregulation of CD20 by NF-κB inhibitors support a direct transcriptional effect. Ex vivo, tumor cells from patients on ibrutinib were less susceptible to anti-CD20 mAb-mediated complement-dependent cytotoxicity than pretreatment cells (median reduction 75%, P &lt; 0.001); however, opsonization by the complement protein C3d, which targets cells for phagocytosis, was relatively maintained. Expression of decay-accelerating factor (CD55) decreased on ibrutinib, providing a likely mechanism for the preserved C3d opsonization. In addition, ibrutinib significantly inhibited trogocytosis, a major contributor to antigen loss and tumor escape during mAb therapy.
Conclusions: Our data indicate that ibrutinib promotes both positive and negative interactions with anti-CD20 mAbs, suggesting that successfully harnessing maximal antitumor effects of such combinations requires further investigation. Clin Cancer Res; 22(1); 86–95. ©2015 AACR.
Accuracy and Usability of a Self-Administered 6-Minute Walk Test Smartphone Application
Authors: Brooks Gabriel C. , Vittinghoff Eric , Iyer Sivaraman , Tandon Damini , Kuhar Peter , Madsen Kristine A. , Marcus Gregory M. , Pletcher Mark J. , Olgin Jeffrey E. 
Published: August 2015

Background—
The 6-minute walk test (6MWT) independently predicts congestive heart failure severity, death, and heart failure hospitalizations, but must be administered in clinic by qualified staff on a premeasured course. As part of the Health eHeart Study, we sought to develop and validate a self-administered 6MWT mobile application (SA-6MWTapp) for independent use at home by patients.

Methods and Results—
We performed a validation study of an SA-6MWTapp in 103 participants. In phase 1 (n=52), we developed a distance-estimation algorithm for the SA-6MWTapp by comparing step counts from an Actigraph and measured distance on a premeasured 6MWT course with step counts and estimated distance obtained simultaneously from our SA-6MWTapp (best estimation algorithm, r=0.89 [95% confidence interval 0.78–0.99]). In phase 2, 32 participants (including those with congestive heart failure and pulmonary hypertension) used the SA-6MWTapp independently in clinic, and the distance estimated by the SA-6MWTapp was compared with the measured distance (r=0.83 [95% confidence interval 0.79–0.92]). In phase 3, 19 patients with congestive heart failure and pulmonary hypertension consecutively enrolled from clinic performed 3.2±1 SA-6MWTapp tests per week at home over 2 weeks. Distances estimated from the SA-6MWTapp during home 6MWTs were highly repeatable (coefficient of variation =4.6%) and correlated with in-clinic–measured distance (r=0.88 [95% confidence interval 0.87–0.89]). Usability surveys performed during the second (in-clinic) and third (at-home) phases demonstrated that the SA-6MWTapp was simple and easy to use independently.

Conclusions—
An SA-6MWTapp is easy to use and yields accurate repeatable measurements in the clinic and at home.
Oscillations or Synchrony? Disruption of Neural Synchrony despite Enhanced Gamma Oscillations in a Model of Disrupted Perceptual Coherence
Authors: Castelhano João , Bernardino Inês , Rebola José , Rodriguez Eugenio , Castelo-Branco Miguel 
Published: August 2015

Abstract
It has been hypothesized that neural synchrony underlies perceptual coherence. The hypothesis of loss of central perceptual coherence has been proposed to be at the origin of abnormal cognition in autism spectrum disorders and Williams syndrome, a neurodevelopmental disorder linked with autism, and a clearcut model for impaired central coherence. We took advantage of this model of impaired holistic processing to test the hypothesis that loss of neural synchrony plays a separable role in visual integration using EEG and a set of experimental tasks requiring coherent integration of local elements leading to 3-D face perception. A profound reorganization of brain activity was identified. Neural synchrony was reduced across stimulus conditions, and this was associated with increased amplitude modulation at 25–45 Hz. This combination of a dramatic loss of synchrony despite increased oscillatory activity is strong evidence that synchrony underlies central coherence. This is the first time, to our knowledge, that dissociation between amplitude and synchrony is reported in a human model of impaired perceptual coherence, suggesting that loss of phase coherence is more directly related to disruption of holistic perception.
Steady-state BOLD Response to Higher-order Cognition Modulates Low-Frequency Neural Oscillations
Authors: Wang Yi-Feng , Dai Gang-Shu , Liu Feng , Long Zhi-Liang , Yan Jin H. , Chen Hua-Fu 
Published: August 2015

AbstractSteady-state responses (SSRs) reflect the synchronous neural oscillations evoked by noninvasive and consistently repeated stimuli at the fundamental or harmonic frequencies. The steady-state evoked potentials (SSEPs; the representative form of the SSRs) have been widely used in the cognitive and clinical neurosciences and brain–computer interface research. However, the steady-state evoked potentials have limitations in examining high-frequency neural oscillations and basic cognition. In addition, synchronous neural oscillations in the low frequency range (&lt;1 Hz) and in higher-order cognition have received a little attention. Therefore, we examined the SSRs in the low frequency range using a new index, the steady-state BOLD responses (SSBRs) evoked by semantic stimuli. Our results revealed that the significant SSBRs were induced at the fundamental frequency of stimuli and the first harmonic in task-related regions, suggesting the enhanced variability of neural oscillations entrained by exogenous stimuli. The SSBRs were independent of neurovascular coupling and characterized by sensorimotor bias, an indication of regional-dependent neuroplasticity. Furthermore, the amplitude of SSBRs may predict behavioral performance and show the psychophysiological relevance. Our findings provide valuable insights into the understanding of the SSRs evoked by higher-order cognition and how the SSRs modulate low-frequency neural oscillations.
Electrophysiological and Kinematic Correlates of Communicative Intent in the Planning and Production of Pointing Gestures and Speech
Authors: Peeters David , Chu Mingyuan , Holler Judith , Hagoort Peter , Özyürek Aslı 
Published: August 2015

AbstractIn everyday human communication, we often express our communicative intentions by manually pointing out referents in the material world around us to an addressee, often in tight synchronization with referential speech. This study investigated whether and how the kinematic form of index finger pointing gestures is shaped by the gesturer's communicative intentions and how this is modulated by the presence of concurrently produced speech. Furthermore, we explored the neural mechanisms underpinning the planning of communicative pointing gestures and speech. Two experiments were carried out in which participants pointed at referents for an addressee while the informativeness of their gestures and speech was varied. Kinematic and electrophysiological data were recorded online. It was found that participants prolonged the duration of the stroke and poststroke hold phase of their gesture to be more communicative, in particular when the gesture was carrying the main informational burden in their multimodal utterance. Frontal and P300 effects in the ERPs suggested the importance of intentional and modality-independent attentional mechanisms during the planning phase of informative pointing gestures. These findings contribute to a better understanding of the complex interplay between action, attention, intention, and language in the production of pointing gestures, a communicative act core to human interaction.
Competition between Mutually Exclusive Object States in Event Comprehension
Authors: Solomon Sarah H. , Hindy Nicholas C. , Altmann Gerry T. M. , Thompson-Schill Sharon L. 
Published: August 2015

Abstract
Successful language comprehension requires one to correctly match symbols in an utterance to referents in the world, but the rampant ambiguity present in that mapping poses a challenge. Sometimes the ambiguity lies in which of two (or more) types of things in the world are under discussion (i.e., lexical ambiguity); however, even a word with a single sense can have an ambiguous referent. This ambiguity occurs when an object can exist in multiple states. Here, we consider two cases in which the presence of multiple object states may render a single-sense word ambiguous. In the first case, one must disambiguate between two states of a single object token in a short discourse. In the second case, the discourse establishes two different tokens of the object category. Both cases involve multiple object states: These states are mutually exclusive in the first case, whereas in the second case, these states can logically exist at the same time. We use fMRI to contrast same-token and different-token discourses, using responses in left posterior ventrolateral prefrontal cortex (pVLPFC) as an indicator of conflict. Because the left pVLPFC is sensitive to competition between multiple, incompatible representations, we predicted that state ambiguity should engender conflict only when those states are mutually exclusive. Indeed, we find evidence of conflict in same-token, but not different-token, discourses. Our data support a theory of left pVLPFC function in which general conflict resolution mechanisms are engaged to select between multiple incompatible representations that arise in many kinds of ambiguity present in language.
<strong>Synopsis der Gattung <em>Rhizogonium</em> (Musci, Rhizogoniaceae)</strong>
Authors: Frahm Jan- Peter , Borchardt Peter , Schramm Michaell , Sonntag Matthias 
Published: August 2015

All species of rhe genus Rhizogonium are keyed out, described and illustrated. Rhizogonium sublimbatum Crum is regarded as synonymous with Rh. novae-hollandiae.
Multipoint Monin–Obukhov Similarity and Its Application to Turbulence Spectra in the Convective Atmospheric Surface Layer
Authors: Tong Chenning , Nguyen Khuong X. 
Published: August 2015

Abstract
A generalized Monin–Obukhov similarity hypothesis for the atmospheric surface layer is proposed. It employs the Monin–Obukhov length as a length scale in both the horizontal and vertical directions, in contrast to the original Monin–Obukhov similarity. Therefore, the horizontal turbulence scales, which are contained in multipoint statistics, must be explicitly included. The similarity hypothesis is formulated for the joint probability density function (JPDF) of multipoint velocity and temperature differences and is termed the multipoint Monin–Obukhov similarity (MMO). In MMO, the nondimensional JPDF in the surface layer depends on the separation vectors and the heights from the ground, both nondimensionalized by the Monin–Obukhov length. A key aspect of MMO is that at heights much smaller than the absolute value of the Monin–Obukhov length, both shear and buoyancy can be important. As an application, MMO is used to predict the two-dimensional horizontal turbulence spectra in the convective surface layer. It predicts a two-layer structure with three scaling ranges. Comparisons of the predicted spectra with those obtained using high-resolution large-eddy simulations show general agreement, supporting MMO. Within MMO, full similarity is only achieved for multipoint statistics, while similarity properties (or a lack thereof) for one-point statistics (the original Monin–Obukhov similarity) can be derived from those of multipoint statistics. MMO provides a new framework for analyzing the turbulence statistics and for understanding the dynamics in the atmospheric surface layer.
Boreal Winter MJO Teleconnection in the Community Atmosphere Model Version 5 with the Unified Convection Parameterization
Authors: Yoo Changhyun , Park Sungsu , Kim Daehyun , Yoon Jin-Ho , Kim Hye-Mi 
Published: August 2015

Abstract
The Madden–Julian oscillation (MJO), the dominant mode of tropical intraseasonal variability, influences weather and climate in the extratropics through atmospheric teleconnection. In this study, two simulations using the Community Atmosphere Model version 5 (CAM5)—one with the default shallow and deep convection schemes and the other with the unified convection scheme (UNICON)—are employed to examine the impacts of cumulus parameterizations on the simulation of the boreal wintertime MJO teleconnection in the Northern Hemisphere. It is demonstrated that the UNICON substantially improves the MJO teleconnection. When the UNICON is employed, the simulated circulation anomalies associated with the MJO better resemble the observed counterpart, compared to the simulation with the default convection schemes. Quantitatively, the pattern correlation for the 300-hPa geopotential height anomalies between the simulations and observation increases from 0.07 for the default schemes to 0.54 for the UNICON. These circulation anomalies associated with the MJO further help to enhance the surface air temperature and precipitation anomalies over North America, although room for improvement is still evident. Initial value calculations suggest that the realistic MJO teleconnection with the UNICON is not due to the changes in the background wind, but rather primarily to the improved tropical convective heating associated with the MJO.