bluuebunny/crossref_metadata_2025_split huggingface dataset:
The First Histidine Triad Motif of PhtD Is Critical for Zinc Homeostasis in
Streptococcus pneumoniae
Authors: Eijkelkamp Bart A. , Pederick Victoria G. , Plumptre Charles D. , Harvey Richard M. , Hughes Catherine E. , Paton James C. , McDevitt Christopher A. 
Published: November 2015

ABSTRACT

Streptococcus pneumoniae
is the world's foremost human pathogen. Acquisition of the first row transition metal ion zinc is essential for pneumococcal colonization and disease. Zinc is acquired via the ATP-binding cassette transporter AdcCB and two zinc-binding proteins, AdcA and AdcAII. We have previously shown that AdcAII is reliant upon the polyhistidine triad (Pht) proteins to aid in zinc recruitment. Pht proteins generally contain five histidine (His) triad motifs that are believed to facilitate zinc binding and therefore play a significant role in pneumococcal metal ion homeostasis. However, the importance and potential redundancy of these motifs have not been addressed. We examined the effects of mutating each of the five His triad motifs of PhtD. The combination of
in vitro
growth assays, active zinc uptake, and PhtD expression studies show that the His triad closest to the protein's amino terminus is the most important for zinc acquisition. Intriguingly,
in vivo
competitive infection studies investigating the amino- and carboxyl-terminal His triad mutants indicate that the motifs have similar importance in colonization. Collectively, our new insights into the contributions of the individual His triad motifs of PhtD, and by extension the other Pht proteins, highlight the crucial role of the first His triad site in zinc acquisition. This study also suggests that the Pht proteins likely play a role beyond zinc acquisition in pneumococcal virulence.
MglC, a Paralog of Myxococcus xanthus GTPase-Activating Protein MglB, Plays a Divergent Role in Motility Regulation
Authors: McLoon Anna L. , Wuichet Kristin , Häsler Michael , Keilberg Daniela , Szadkowski Dobromir , Søgaard-Andersen Lotte 
Published: November 2015

ABSTRACT

In order to optimize interactions with their environment and one another, bacteria regulate their motility. In the case of the rod-shaped cells of
Myxococcus xanthus
, regulated motility is essential for social behaviors.
M. xanthus
moves over surfaces using type IV pilus-dependent motility and gliding motility. These two motility systems are coordinated by a protein module that controls cell polarity and consists of three polarly localized proteins, the small G protein MglA, the cognate MglA GTPase-activating protein MglB, and the response regulator RomR. Cellular reversals are induced by the Frz chemosensory system, and the output response regulator of this system, FrzZ, interfaces with the MglA/MglB/RomR module to invert cell polarity. Using a computational approach, we identify a paralog of MglB, MXAN_5770 (MglC). Genetic epistasis experiments demonstrate that MglC functions in the same pathway as MglA, MglB, RomR, and FrzZ and is important for regulating cellular reversals. Like MglB, MglC localizes to the cell poles asymmetrically and with a large cluster at the lagging pole. Correct polar localization of MglC depends on RomR and MglB. Consistently, MglC interacts directly with MglB and the C-terminal output domain of RomR, and we identified a surface of MglC that is necessary for the interaction with MglB and for MglC function. Together, our findings identify an additional member of the
M. xanthus
polarity module involved in regulating motility and demonstrate how gene duplication followed by functional divergence can add a layer of control to the complex cellular processes of motility and motility regulation.

IMPORTANCE
Gene duplication and the subsequent divergence of the duplicated genes are important evolutionary mechanisms for increasing both biological complexity and regulation of biological processes. The bacterium
Myxococcus xanthus
is a soil bacterium with an unusually large genome that carries out several social processes, including predation of other bacterial species and formation of multicellular, spore-filled fruiting bodies. One feature of the large
M. xanthus
genome is that it contains many gene duplications. Here, we compare the products of one example of gene duplication and divergence, in which a paralog of the cognate MglA GTPase-activating protein MglB has acquired a different and opposing role in the regulation of cellular polarity and motility, processes critical to the bacterium's social behaviors.
Differentiating between detrimental and beneficial interruptions: a mixed-methods study
Authors: Myers Robert A , McCarthy Mary C , Whitlatch Amelia , Parikh Pratik J 
Published: November 2015

IntroductionEfforts to understand interruptions now span much of the last decade and a half. Often thought to negatively impact patient safety, some now acknowledge that interruptions may be beneficial and actually necessary for safety and high quality care. This study seeks a framework for differentiating between interruptions that are detrimental and those that are beneficial.MethodsA mixed-methods approach at a US Level 1 trauma centre included direct observation of 13 registered nurses (RNs), survey of 47 RNs, retrospective observation of hands-free communication devices, and modelling of observed interruptions to key performance measures.ResultsOn average, RNs were interrupted every 11 min, with 20.3% of their workload triggered by interruptions. While 85% of RNs agreed that interruptions place their patients at risk, only 21% agreed that all should be eliminated. During one 90-min period, 18 original events spawned 68 interruptions, 50 of these repeat messages. A statistical model, with patient measures of time and comfort, revealed that alarms and call lights returning RN's attention to the patient outside the patient room are beneficial, while interruptions in the patient room are generally detrimental. Triangulating the results, we present an emerging framework for differentiating between beneficial and detrimental interruptions based on the impact of interruptions on the RN's steady treatment and attention to the patient.ConclusionsA mixed-methods approach can help distinguish between detrimental and beneficial interruptions. While interruptions breaking the delivery of steady treatment and attention to the patient are detrimental, those returning the RN's focus to the patient, as well as those supporting patient-clinician and clinician-clinician communications are beneficial. This insight may be helpful to healthcare delivery teams tasked with improving interruption-laden processes.
Transport and magnetic properties of Heusler alloy Ni–Mn–Sb prepared by solid state microwave heating
Authors: Chen Bin , Zhu Hanming , Shi Yunfeng , Yue Song 
Published: November 2015

In this study, Heusler alloy [Formula: see text] has been prepared by solid state hybrid microwave heating within 40 min. X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) analyses reveal that the obtained samples are of single phase cubic structure and homogeneous. Temperature-dependence of electrical resistivity and magnetization measurements confirm the austenite to martensitic transition of the first-order nature with the absence of the exchange bias (EB), which is verified by the magnetic hysteresis loops. Compared with the samples prepared by conventional arc-melting method, the sample synthesized by fast microwave heating has lower martensitic transition temperature, smooth magnetization change in the martensitic region and disappeared EB, implying strongly suppressed antiferromagnetic (AFM) interaction. These results suggest that tuning the microstructure via different synthesis method can influence significantly the martensitic transition and magnetic interactions in the Ni–Mn–Sb system.
miR-124 and Androgen Receptor Signaling Inhibitors Repress Prostate Cancer Growth by Downregulating Androgen Receptor Splice Variants, EZH2, and Src
Authors: Shi Xu-Bao , Ma Ai-Hong , Xue Lingru , Li Meimei , Nguyen Hao G. , Yang Joy C. , Tepper Clifford G. , Gandour-Edwards Regina , Evans Christopher P. , Kung Hsing-Jien , deVere White Ralph W. 
Published: November 2015

Abstract
miR-124 targets the androgen receptor (AR) transcript, acting as a tumor suppressor to broadly limit the growth of prostate cancer. In this study, we unraveled the mechanisms through which miR-124 acts in this setting. miR-124 inhibited proliferation of prostate cancer cells in vitro and sensitized them to inhibitors of androgen receptor signaling. Notably, miR-124 could restore the apoptotic response of cells resistant to enzalutamide, a drug approved for the treatment of castration-resistant prostate cancer. We used xenograft models to examine the effects of miR-124 in vivo when complexed with polyethylenimine-derived nanoparticles. Intravenous delivery of miR-124 was sufficient to inhibit tumor growth and to increase tumor cell apoptosis in combination with enzalutamide. Mechanistic investigations revealed that miR-124 directly downregulated AR splice variants AR-V4 and V7 along with EZH2 and Src, oncogenic targets that have been reported to contribute to prostate cancer progression and treatment resistance. Taken together, our results offer a preclinical rationale to evaluate miR-124 for cancer treatment. Cancer Res; 75(24); 5309–17. ©2015 AACR.
Disseminated Tumor Cells Persist in the Bone Marrow of Breast Cancer Patients through Sustained Activation of the Unfolded Protein Response
Authors: Bartkowiak Kai , Kwiatkowski Marcel , Buck Friedrich , Gorges Tobias M. , Nilse Lars , Assmann Volker , Andreas Antje , Müller Volkmar , Wikman Harriet , Riethdorf Sabine , Schlüter Hartmut , Pantel Klaus 
Published: November 2015

Abstract
Disseminated tumor cells (DTC), which share mesenchymal and epithelial properties, are considered to be metastasis-initiating cells in breast cancer. However, the mechanisms supporting DTC survival are poorly understood. DTC extravasation into the bone marrow may be encouraged by low oxygen concentrations that trigger metabolic and molecular alterations contributing to DTC survival. Here, we investigated how the unfolded protein response (UPR), an important cytoprotective program induced by hypoxia, affects the behavior of stressed cancer cells. DTC cell lines established from the bone marrow of patients with breast cancer (BC-M1), lung cancer, (LC-M1), and prostate cancer (PC-E1) were subjected to hypoxic and hypoglycemic conditions. BC-M1 and LC-M1 exhibiting mesenchymal and epithelial properties adapted readily to hypoxia and glucose starvation. Upregulation of UPR proteins, such as the glucose-regulated protein Grp78, induced the formation of filamentous networks, resulting in proliferative advantages and sustained survival under total glucose deprivation. High Grp78 expression correlated with mesenchymal attributes of breast and lung cancer cells and with poor differentiation in clinical samples of primary breast and lung carcinomas. In DTCs isolated from bone marrow specimens from breast cancer patients, Grp78-positive stress granules were observed, consistent with the likelihood these cells were exposed to acute cell stress. Overall, our findings provide the first evidence that the UPR is activated in DTC in the bone marrow from cancer patients, warranting further study of this cell stress pathway as a predictive biomarker for recurrent metastatic disease. Cancer Res; 75(24); 5367–77. ©2015 AACR.
Changes in Climate Extremes and Catastrophic Events in the Mongolian Plateau from 1951 to 2012
Authors: Wang Lei , Yao Zhi-Jun , Jiang Li-Guang , Wang Rui , Wu Shan-Shan , Liu Zhao-Fei 
Published: November 2015

AbstractThe spatiotemporal changes in 21 indices of extreme temperature and precipitation for the Mongolian Plateau from 1951 to 2012 were investigated on the basis of daily temperature and precipitation data from 70 meteorological stations. Changes in catastrophic events, such as droughts, floods, and snowstorms, were also investigated for the same period. The correlations between catastrophic events and the extreme indices were examined. The results show that the Mongolian Plateau experienced an asymmetric warming trend. Both the cold extremes and warm extremes showed greater warming at night than in the daytime. The spatial changes in significant trends showed a good homogeneity and consistency in Inner Mongolia. Changes in the precipitation extremes were not as obvious as those in the temperature extremes. The spatial distributions in changes of precipitation extremes were complex. A decreasing trend was shown for total precipitation from west to east as based on the spatial distribution of decadal trends. Drought was the most serious extreme disaster, and prolonged drought for longer than 3 yr occurred about every 7–11 yr. An increasing trend in the disaster area was apparent for flood events from 1951 to 2012. A decreasing trend was observed for the maximum depth of snowfall from 1951 to 2012, with a decreased average maximum depth of 10 mm from the 1990s.
Clouds and the Atmospheric Circulation Response to Warming
Authors: Ceppi Paulo , Hartmann Dennis L. 
Published: November 2015

Abstract
The authors study the effect of clouds on the atmospheric circulation response to CO2 quadrupling in an aquaplanet model with a slab ocean lower boundary. The cloud effect is isolated by locking the clouds to either the control or 4xCO2 state in the shortwave (SW) or longwave (LW) radiation schemes. In the model, cloud radiative changes explain more than half of the total poleward expansion of the Hadley cells, midlatitude jets, and storm tracks under CO2 quadrupling, even though they cause only one-fourth of the total global-mean surface warming. The effect of clouds on circulation results mainly from the SW cloud radiative changes, which strongly enhance the equator-to-pole temperature gradient at all levels in the troposphere, favoring stronger and poleward-shifted midlatitude eddies. By contrast, quadrupling CO2 while holding the clouds fixed causes strong polar amplification and weakened midlatitude baroclinicity at lower levels, yielding only a small poleward expansion of the circulation. The results show that 1) the atmospheric circulation responds sensitively to cloud-driven changes in meridional and vertical temperature distribution and 2) the spatial structure of cloud feedbacks likely plays a dominant role in the circulation response to greenhouse gas forcing. While the magnitude and spatial structure of the cloud feedback are expected to be highly model dependent, an analysis of 4xCO2 simulations of CMIP5 models shows that the SW cloud feedback likely forces a poleward expansion of the tropospheric circulation in most climate models.
Comparison of Distributional Statistics of Aquarius and Argo Sea Surface Salinity Measurements
Authors: Mannshardt Elizabeth , Sucic Katarina , Fuentes Montserrat , Bingham Frederick M. 
Published: November 2015

AbstractSalinity is an indicator of the interaction between ocean circulation and the global water cycle, which in turn affects the regulation of the earth’s climate. To thoroughly understand sea surface salinity’s connection to processes that define the hydrological cycle, such as surface forcing and ocean mixing, there is need for proper validation of remotely sensed salinity products with independent measurements, beyond central tendencies, across the entire distribution of salinity. Because of its fine spatial and temporal coverage, Aquarius presents an ideal measurement system for fully characterizing the distribution and properties of sea surface salinity. Using the first 33 months of Aquarius, version 3.0, level 2 sea surface salinity data, both central tendencies and distributional quantile characteristics across time and space are investigated, and a statistical validation of Aquarius measurements with Argo in situ observations is conducted. Several aspects are considered, including regional characteristics and temporal agreement, as well as seasonal differences by ocean basin and hemisphere. Regional studies examine the time and space scales of variability through time series comparisons and an analysis of quantile properties. Results indicate that there are significant differences between the tails of their respective distributions, especially the lower tail. The Aquarius data show longer, fatter lower tails, indicating higher probability to sample low-salinity events. There is also evidence of differences in measurement variation between Aquarius and Argo. These results are seen across seasons, ocean basins, hemispheres, and regions.
The Influence of Land Surface Heterogeneities on Heavy Convective Rainfall in the Baltimore–Washington Metropolitan Area
Authors: Ryu Young-Hee , Smith James A. , Bou-Zeid Elie , Baeck Mary L. 
Published: November 2015

Abstract
Low-level convergence induced by land surface heterogeneities can have substantial influence on atmospheric convection and rainfall. Analyses of heavy convective rainfall in the Baltimore–Washington metropolitan area are performed using the Weather Research and Forecasting (WRF) Model, coupled with the Princeton Urban Canopy Model (PUCM) that resolves urban subfacet heterogeneity. Analyses center on storms that produced heavy rainfall and record urban flooding in Baltimore on 1 June 2012. The control simulation using PUCM shows a better performance in reproducing the surface energy balance and rainfall than the simulation using a traditional slab model for the urban area. Sensitivity experiments are carried out to identify the role of the land surface heterogeneities, arising from land–water and urban–nonurban contrasts in the Baltimore–Washington metropolitan area, on heavy rainfall from organized thunderstorm systems. The intersection of low-level convergence zones from thunderstorm downdrafts and from the bay breeze from the Chesapeake Bay enhances the upward motion of preexisting convective storms. The larger sensible heating from the urban area modifies the low-level temperature and wind fields, which in turn modifies the bay breeze. The enhanced moisture supply in the deepened bay-breeze inflow layer due to urban heating promotes intense convection and heavy rainfall in conjunction with the enhanced upward motion at intersecting convergence zones. This study suggests that better representations of surface heat and moisture fluxes in urban areas along major water bodies are required to better capture the timing and location of severe thunderstorms and heavy rainfall.
Comparison of Knee Kinematics After Single-Bundle Anterior Cruciate Ligament Reconstruction via the Medial Portal Technique With a Central Femoral Tunnel and an Eccentric Femoral Tunnel and After Anatomic Double-Bundle Reconstruction
Authors: Herbort Mirco , Domnick Christoph , Raschke Michael Johannes , Lenschow Simon , Förster Tim , Petersen Wolf , Zantop Thore 
Published: November 2015

Background: Anatomic femoral tunnel placement in anterior cruciate ligament (ACL) reconstruction is considered to be a key to good primary stability of the knee. There is still no consensus on whether a centrally placed single bundle in the anatomical femoral footprint can compare with anatomic double-bundle (DB) reconstruction. Purpose/Hypothesis: The purpose of this study was to determine knee kinematics after single-bundle ACL reconstruction via the medial portal technique using 2 different femoral tunnel positions and to compare results with those of the anatomic DB technique. The hypotheses were that (1) single-bundle reconstruction using the medial portal technique with a centrally placed femoral tunnel relative to the native footprint (SB-central technique) would more closely restore intact knee kinematics compared with the same reconstruction technique with an eccentric femoral tunnel drilled in the anteromedial bundle footprint (SB-AM technique) and (2) DB reconstruction would result in superior kinematics compared with the SB-central technique. Study Design: Controlled laboratory study. Methods: Knee kinematics was examined in 10 fresh-frozen human cadaveric knees using a robotic/universal force-moment sensor system. Kinematics in simulated pivot-shift and 134-N anterior tibial loading tests were determined in different conditions within the same specimen: (1) intact ACL, (2) deficient ACL, (3) SB-AM, (4) SB-central, and (5) DB. Results: All reconstruction techniques significantly reduced anterior tibial translation (ATT) compared with a deficient ACL at 0°, 15°, 30°, 60°, and 90° in the anterior tibial loading test ( P < .01, repeated-measures analysis of variance) and at 0°, 15°, and 30° in the simulated pivot-shift test ( P < .001). There were no significant differences in the SB-central group and the DB group compared with the intact ACL. Reconstruction in the SB-AM group resulted in significantly increased ATT compared with the intact ACL in near-to-extension angles in both tests (0°, 15°, and 30°; P < .01). SB-central and DB reconstructions both resulted in significantly reduced ATT, in some tests at ≤30°, compared with SB-AM reconstruction ( P < .05). No significant differences between the SB-central and DB groups were found ( P > .05). Conclusion: The SB-central technique restored intact knee kinematics more closely than did SB-AM reconstruction at time zero. There were no differences in knee kinematics between the DB and SB-central techniques. Clinical Relevance: Anatomic single-bundle ACL reconstruction provides similar knee kinematics as anatomic double-bundle reconstruction.
Effect of deslorelin on testicular function, serum dihydrotestosterone and oestradiol concentrations during and after suppression of sexual activity in tom cats
Authors: Gültiken Nilgün , Aslan Selim , Ay Serhan Serhat , Gülbahar Mustafa Yavuz , Thuróczy Julianna , Koldaş Ece , Kaya Duygu , Fındık Murat , Schäfer-Somi Sabine 
Published: November 2015

Objectives The aim of the study was to evaluate the efficacy of a 4.7 mg deslorelin implant in tom cats. Methods Nine mature male cats were included in the deslorelin group and five cats in the control group. Before the study started, all cats were confirmed to have distinct sexually dimorphic behaviour. Blood samples were taken on the implantation day, at day 7 and at day 15, then monthly, in order to measure serum dihydrotestosterone (DHT) and 17beta(β)-oestradiol concentrations. The deslorelin group (n = 9) was divided into two subgroups: five cats (cats 1–5) were neutered in the postimplantation period during suppression of sexually dimorphic behaviour, and four cats (cats 6–9) were neutered after re-expression of sexually dimorphic behaviour. The control group cats (n = 5) were castrated without administration of the implant. Results Sexually dimorphic behaviours ceased within a mean ± SD of 13–58 days (23.30 ± 14.17) after implantation. DHT concentration decreased within 30 days. The mean duration of suppression was 26.5 ± 7.42 months and reactivation coincided with increased DHT values reaching preimplantation concentrations within 1 month. 17β-oestradiol concentrations significantly correlated with DHT concentrations ( P <0.01). For cats castrated during suppression of sexual behaviour, the length of the long axes of the nuclei of Leydig cells, the diameter of seminiferous tubules and the height of the epithelium of the seminiferous tubules did not change until 3–6 months after implantation, whereas at 12 and 32 months the measured values were even lower than in the control group. For cats castrasted after reactivation, the length of long axes of the nuclei of Leydig cells and the diameter of seminiferous tubules approached the values of the control group between 4 and 6 months after reactivation. Conclusions and relevance A deslorelin implant (4.7 mg) suppresses sexually dimorphic behaviour in tom cats without any side effects and with full reversibility; however, duration of suppression is highly individual.