bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Engineered PreQ1 Riboswitches for Inducible Gene Regulation in Mycobacteria
Authors: Van Vlack Erik R. , Topp Shana , Seeliger Jessica C. 
Published: January 2017

ABSTRACT

We report here the behavior of naturally occurring and rationally engineered preQ1 riboswitches and their application to inducible gene regulation in mycobacteria. Because mycobacteria lack preQ1 biosynthetic genes, we hypothesized that preQ1 could be used as an exogenous nonmetabolite ligand to control riboswitches in mycobacteria. Selected naturally occurring preQ1 riboswitches were assayed and successfully drove preQ1-dependent repression of a green fluorescent protein reporter in
Mycobacterium smegmatis
. Using structure-based design, we engineered three preQ1 riboswitches from
Thermoanaerobacter tencongensis
,
Bacillus subtilis
, and
Lactobacillus rhamnosus
toward achieving higher response ratios and increased repression. Assuming a steady-state model, variants of the
T. tencongensis
riboswitch most closely followed the predicted trends. Unexpectedly, the preQ1 dose response was best described by a model with a second, independent preQ1 binding site. This behavior was general to the preQ1 riboswitch family, since the wild type and rationally designed mutants of riboswitches from all three bacteria behaved analogously. Across all variants, the response ratios, which describe expression in the absence versus the presence of preQ1, ranged from <2 to ∼10, but repression in all cases was incomplete up to 1 mM preQ1. By reducing the transcript expression level, we obtained a preQ1 riboswitch variant appropriate for inducible knockdown applications. We further showed that the preQ1 response is reversible, is titratable, and can be used to control protein expression in mycobacteria within infected macrophages. By engineering naturally occurring preQ1 riboswitches, we have not only extended the tools available for inducible gene regulation in mycobacteria but also uncovered new behavior of these riboswitches.

IMPORTANCE
Riboswitches are elements found in noncoding regions of mRNA that regulate gene expression, typically in response to an endogenous metabolite. Riboswitches have emerged as important tools for inducible gene expression in diverse organisms. We noted that mycobacteria lack the biosynthesis genes for preQ1, a ligand for riboswitches from diverse bacteria. Predicting that preQ1 is not present in mycobacteria, we showed that it controls optimized riboswitches appropriate for gene knockdown applications. Further, the riboswitch response is subject to a second independent preQ1 binding event that has not been previously documented. By engineering naturally occurring riboswitches, we have uncovered a new behavior, with implications for riboswitch function in its native context, and extended the tools available for inducible gene regulation in mycobacteria.
ArtA-Dependent Processing of a Tat Substrate Containing a Conserved Tripartite Structure That Is Not Localized at the C Terminus
Authors: Abdul Halim Mohd Farid , Stoltzfus Jonathan D. , Schulze Stefan , Hippler Micheal , Pohlschroder Mechthild 
Published: January 2017

ABSTRACT

Most prokaryote-secreted proteins are transported to the cell surface using either the general secretion (Sec) or twin-arginine translocation (Tat) pathway. A majority of secreted proteins are anchored to the cell surface, while the remainder are released into the extracellular environment. The anchored surface proteins play a variety of important roles in cellular processes, ranging from facilitating interactions between cells to maintaining cell stability. The extensively studied S-layer glycoprotein (SLG) of
Haloferax volcanii
, previously thought to be anchored via C-terminal intercalation into the membrane, was recently shown to be lipidated and to have its C-terminal segment removed in processes dependent upon archaeosortase A (ArtA), a recently discovered enzyme. While SLG is a Sec substrate,
in silico
analyses presented here reveal that, of eight additional ArtA substrates predicted, two substrates also contain predicted Tat signal peptides, including Hvo_0405, which has a highly conserved tripartite structure that lies closer to the center of the protein than to its C terminus, unlike other predicted ArtA substrates identified to date. We demonstrate that, even given its atypical location, this tripartite structure, which likely resulted from the fusion of genes encoding an ArtA substrate and a cytoplasmic protein, is processed in an ArtA-dependent manner. Using an Hvo_0405 mutant lacking the conserved “twin” arginines of the predicted Tat signal peptide, we show that Hvo_0405 is indeed a Tat substrate and that ArtA substrates include both Sec and Tat substrates. Finally, we confirmed the Tat-dependent localization and signal peptidase I (SPase I) cleavage site of Hvo_0405 using mass spectrometry.

IMPORTANCE
The specific mechanisms that facilitate protein anchoring to the archaeal cell surface remain poorly understood. Here, we have shown that the proteins bound to the cell surface of the model archaeon
H. volcanii
, through a recently discovered novel ArtA-dependent anchoring mechanism, are more structurally diverse than was previously known. Specifically, our results demonstrate that both Tat and Sec substrates, which contain the conserved tripartite structure of predicted ArtA substrates, can be processed in an ArtA-dependent manner and that the tripartite structure need not lie near the C terminus for this processing to occur. These data improve our understanding of archaeal cell biology and are invaluable for
in silico
subcellular localization predictions of archaeal and bacterial proteins.
A rapid lake-shallowing event terminated preservation of the Miocene Clarkia Fossil Konservat-Lagerstätte (Idaho, USA)
Authors: Wang Huanye , Leng Qin , Liu Weiguo , Yang Hong 
Published: January 2017

Abstract
The world-renowned middle Miocene Clarkia lacustrine deposits (15.4–16.0 Ma) in northern Idaho, United States, known as Fossil Lagerstätten, yield extraordinary fossils that preserve in situ ancient biomolecules and organic biomarkers. The sudden formation of the Clarkia Lake basin by means of the Columbia River Basalt damming the proto–St. Maries River is well documented, but less is known about the tempo and mode of the lake environmental succession which impacted on the preservation of these Fossil Lagerstätten. Here, we present evidence for a previously unrecognized, geologically instantaneous drop in the Clarkia Lake water level, using tetraether-based water-depth proxies from a continuous sedimentary sequence at the classic P-33 site. Terrestrial hydrological conditions inferred from compound-specific hydrogen isotope compositions (δD) and tetraether-derived temperature estimates from the same sequence show that the rapid shallowing by &gt;10 m was independent of regional climatic changes. We hypothesize that a volcanic-related geological event was primarily responsible for the rapid reduction of Clarkia Lake water depth—an event that played a decisive role in switching depositional conditions for Clarkia Fossil Lagerstätten from a conservation deposit to a concentration deposit.
Accelerating slip rates on the Puente Hills blind thrust fault system beneath metropolitan Los Angeles, California, USA
Authors: Bergen Kristian J. , Shaw John H. , Leon Lorraine A. , Dolan James F. , Pratt Thomas L. , Ponti Daniel J. , Morrow Eric , Barrera Wendy , Rhodes Edward J. , Murari Madhav K. , Owen Lewis A. 
Published: January 2017

Abstract
Slip rates represent the average displacement across a fault over time and are essential to estimating earthquake recurrence for probabilistic seismic hazard assessments. We demonstrate that the slip rate on the western segment of the Puente Hills blind thrust fault system, which is beneath downtown Los Angeles, California (USA), has accelerated from ∼0.22 mm/yr in the late Pleistocene to ∼1.33 mm/yr in the Holocene. Our analysis is based on syntectonic strata derived from the Los Angeles River, which has continuously buried a fold scarp above the blind thrust. Slip on the fault beneath our field site began during the late-middle Pleistocene and progressively increased into the Holocene. This increase in rate implies that the magnitudes and/or the frequency of earthquakes on this fault segment have increased over time. This challenges the characteristic earthquake model and presents an evolving and potentially increasing seismic hazard to metropolitan Los Angeles.
Forecasting transitions in monogenetic eruptions using the geologic record
Authors: Kereszturi Gábor , Bebbington Mark , Németh Károly 
Published: January 2017

Abstract
Spatial forecasting of volcanism and associated hazards in intraplate monogenetic volcanic fields is subject to large uncertainties in both data and models. We demonstrate a novel logistic regression method for mapping phreatomagmatic-magmatic eruption transition susceptibility using near-surface hydrologic, topographic, and geologic data. The method is illustrated on the Auckland volcanic field, the location of New Zealand’s largest city, Auckland. Environmental factors examined for possible influence included the thickness of water-saturated and porous sediments, substrate type and geology, vent elevation, and distance from the nearest fault. By comparing these factors with the volumes and styles of past eruption sequences, a location-specific eruption sequence forecasting model was constructed, recognizing that larger and/or longer eruptions are more likely to exhaust vent-area sources of water. Estimating volcanic hazard susceptibility in this way allows more effective planning and improved preeruption preparedness between eruptions and during future volcanic crises.
Clinical disease presentation and ECG characteristics ofLMNAmutation carriers
Authors: Ollila Laura , Nikus Kjell , Holmström Miia , Jalanko Mikko , Jurkko Raija , Kaartinen Maija , Koskenvuo Juha , Kuusisto Johanna , Kärkkäinen Satu , Palojoki Eeva , Reissell Eeva , Piirilä Päivi , Heliö Tiina 
Published: January 2017

ObjectiveMutations in theLMNAgene encoding lamins A and C of the nuclear lamina are a frequent cause of cardiomyopathy accounting for 5–8% of familial dilated cardiomyopathy (DCM). Our aim was to study disease onset, presentation and progression amongLMNAmutation carriers.MethodsClinical follow-up data from 27LMNAmutation carriers and 78 patients with idiopathic DCM without anLMNAmutation were collected. In addition, ECG data were collected and analysed systematically from 20 healthy controls.ResultsKaplan-Meier analysis revealed no difference in event-free survival (death, heart transplant, resuscitation and appropriate implantable cardioverter-defibrillator therapy included as events) betweenLMNAmutation carriers and DCM controls (p=0.5).LMNAmutation carriers presented with atrial fibrillation at a younger age than the DCM controls (47 vs 57 years, p=0.003). MaleLMNAmutation carriers presented with clinical manifestations roughly a decade earlier than females. In close follow-up non-sustained ventricular tachycardia was detected in 78% ofLMNAmutation carriers. ECG signs of septal remodelling were present in 81% of theLMNAmutation carriers, 21% of the DCM controls and none of the healthy controls giving a high sensitivity and specificity for the standard ECG in distinguishingLMNAmutation carriers from patients with DCM and healthy controls.ConclusionsMaleLMNAmutation carriers present clinical manifestations at a younger age than females. ECG septal remodelling appears to distinguishLMNAmutation carriers from healthy controls and patients with DCM withoutLMNAmutations.
Does cardiac rehabilitation meet minimum standards: an observational study using UK national audit?
Authors: Doherty Patrick , Salman Ahmad , Furze Gill , Dalal Hasnain M , Harrison Alexander 
Published: January 2017

ObjectiveTo assess the extent by which programmes meet national minimum standards for the delivery of cardiac rehabilitation (CR) as part of the National Certification Programme for Cardiovascular Rehabilitation (NCP_CR).MethodsThe analysis used UK National Audit of Cardiac Rehabilitation (NACR) data extracted and validated for the period 2013–2014 set against six NCP_CR measures deemed as important for the delivery of high-quality CR programmes. Each programme that achieved a single minimum standard was given a score of 1. The range of the scoring for meeting the minimum standards is between 1 and 6. The performance of CR programmes was categorised into three groups: high (score of 5–6), middle (scores of 3–4) and low (scores of 1–2). If a programme did not meet any of the six criteria, they were considered to have failed.ResultsData from 170 CR programmes revealed statistically significant differences among UK CR programmes. The principal findings were that, based on NCP_CR criteria, 30.6% were assessed as high performance with 45.9% as mid-level performance programmes, 18.2% were in the lower-level and 5.3% failed to meet any of the minimum criteria.ConclusionsThis study shows that high levels of performance is achievable in the era of modern cardiology and that many CR programmes are close to meeting high performance standards. However, substantial variation, below the recommended minimum standards, exists throughout the UK. National certification should be seen as a positive step to ensure that patients, irrespective of where they live, are accessing quality services.
Wannier functions and ℤ2 invariants in time-reversal symmetric topological insulators
Authors: Cornean Horia D. , Monaco Domenico , Teufel Stefan 
Published: January 2017

We provide a constructive proof of exponentially localized Wannier functions and related Bloch frames in 1- and 2-dimensional time-reversal symmetric (TRS) topological insulators. The construction is formulated in terms of periodic TRS families of projectors (corresponding, in applications, to the eigenprojectors on an arbitrary number of relevant energy bands), and is thus model-independent. The possibility to enforce also a TRS constraint on the frame is investigated. This leads to a topological obstruction in dimension 2, related to [Formula: see text] topological phases.We review several proposals for [Formula: see text] indices that distinguish these topological phases, including the ones by Fu–Kane [16], Prodan [33], Graf–Porta [24] and Fiorenza–Monaco–Panati [27]. We show that all these formulations are equivalent. In particular, this allows to prove a geometric formula for the [Formula: see text] invariant of 2-dimensional TRS topological insulators, originally indicated in [16], which expresses it in terms of the Berry connection and the Berry curvature.
Nonlinear Control of Flexural–Torsional Vibrations of a Rotating Thin-Walled Composite Beam
Authors: Warminski Jerzy , Latalski Jarosław 
Published: January 2017

In this paper, the effectiveness of a saturation control strategy in suppressing vibration of a rotating composite thin walled beam is studied. The mathematical model of the flexible beam takes into account a shear deformation effect, a warping function, a centrifugal force and the Coriolis acceleration. To extend the generality of the proposed formulation an inertia of the hub is also considered. Adaptive capability of the beam is achieved through the implementation of the saturation control algorithm.Within the performed tests, the discussed control strategy is applied for different magnitudes of flexural–torsional vibration modes resulting from different orientations of beam laminate-reinforcing fiber’s. The obtained results prove the applied nonlinear control to be the effective method for beam vibration suppression in near-by resonance zones for all studied cases. Parametric studies considered different rotating speeds of the system. It is shown that the vibration of the beam can be suppressed to similar levels independently of the transportation motion rotating speed. However, significant differences in the width of vibration suppression zones are observed.
IKBKE Is Required during KRAS-Induced Pancreatic Tumorigenesis
Authors: Rajurkar Mihir , Dang Kyvan , Fernandez-Barrena Maite G. , Liu Xiangfan , Fernandez-Zapico Martin E. , Lewis Brian C. , Mao Junhao 
Published: January 2017

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies lacking effective therapeutic strategies. Here, we show that the noncanonical IκB-related kinase, IKBKE, is a critical oncogenic effector during KRAS-induced pancreatic transformation. Loss of IKBKE inhibits the initiation and progression of pancreatic tumors in mice carrying pancreatic-specific KRAS activation. Mechanistically, we demonstrate that this protumoral effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels of activity of the NF-κB pathway. Further analysis reveals that IKBKE regulates GLI1 nuclear translocation and promotes the reactivation of AKT post-inhibition of mTOR in PDAC cells. Interestingly, combined inhibition of IKBKE and mTOR synergistically blocks pancreatic tumor growth. Together, our findings highlight the functional importance of IKBKE in pancreatic cancer, support the evaluation of IKBKE as a therapeutic target in PDAC, and suggest IKBKE inhibition as a strategy to improve efficacy of mTOR inhibitors in the clinic. Cancer Res; 77(2); 320–9. ©2017 AACR.
Anesthesia Technique and Outcomes of Mechanical Thrombectomy in Patients With Acute Ischemic Stroke
Authors: Bekelis Kimon , Missios Symeon , MacKenzie Todd A. , Tjoumakaris Stavropoula , Jabbour Pascal 
Published: January 2017

Background and Purpose—
The impact of anesthesia technique on the outcomes of mechanical thrombectomy for acute ischemic stroke remains an issue of debate. We investigated the association of general anesthesia with outcomes in patients undergoing mechanical thrombectomy for ischemic stroke.

Methods—
We performed a cohort study involving patients undergoing mechanical thrombectomy for ischemic stroke from 2009 to 2013, who were registered in the New York Statewide Planning and Research Cooperative System database. An instrumental variable (hospital rate of general anesthesia) analysis was used to simulate the effects of randomization and investigate the association of anesthesia technique with case-fatality and length of stay.

Results—
Among 1174 patients, 441 (37.6%) underwent general anesthesia and 733 (62.4%) underwent conscious sedation. Using an instrumental variable analysis, we identified that general anesthesia was associated with a 6.4% increased case-fatality (95% confidence interval, 1.9%–11.0%) and 8.4 days longer length of stay (95% confidence interval, 2.9–14.0) in comparison to conscious sedation. This corresponded to 15 patients needing to be treated with conscious sedation to prevent 1 death. Our results were robust in sensitivity analysis with mixed effects regression and propensity score–adjusted regression models.

Conclusions—
Using a comprehensive all-payer cohort of acute ischemic stroke patients undergoing mechanical thrombectomy in New York State, we identified an association of general anesthesia with increased case-fatality and length of stay. These considerations should be taken into account when standardizing acute stroke care.
Modeling Surface Runoff and Water Fluxes over Contrasted Soils in the Pastoral Sahel: Evaluation of the ALMIP2 Land Surface Models over the Gourma Region in Mali
Authors: Grippa Manuela , Kergoat Laurent , Boone Aaron , Peugeot Christophe , Demarty Jérôme , Cappelaere Bernard , Gal Laetitia , Hiernaux Pierre , Mougin Eric , Ducharne Agnès , Dutra Emanuel , Anderson Martha , Hain Christopher ,   ALMIP2 Working Group
Published: January 2017

Abstract
Land surface processes play an important role in the West African monsoon variability. In addition, the evolution of hydrological systems in this region, and particularly the increase of surface water and runoff coefficients observed since the 1950s, has had a strong impact on water resources and on the occurrence of floods events. This study addresses results from phase 2 of the African Monsoon Multidisciplinary Analysis (AMMA) Land Surface Model Intercomparison Project (ALMIP2), carried out to evaluate the capability of different state-of-the-art land surface models to reproduce surface processes at the mesoscale. Evaluation of runoff and water fluxes over the Mali site is carried out through comparison with runoff estimations over endorheic watersheds as well as evapotranspiration (ET) measurements. Three remote-sensing-based ET products [ALEXI, MODIS, and Global Land Evaporation Amsterdam Model (GLEAM)] are also analyzed. It is found that, over deep sandy soils, surface runoff is generally overestimated, but the ALMIP2 multimodel mean reproduces in situ measurements of ET and water stress events rather well. However, ALMIP2 models are generally unable to distinguish among the two contrasted hydrological systems typical of the study area. Employing as input a soil map that explicitly represents shallow soils improves the representation of water fluxes for the models that can account for their representation. Shallow soils are shown to be also quite challenging for remote-sensing-based ET products, even if their effect on evaporative loss was captured by the diagnostic thermal-based ALEXI. A better representation of these soils, in soil databases, model parameterizations, and remote sensing algorithms, is fundamental to improve the estimation of water fluxes in this part of the Sahel.
Projecting and Attributing Future Changes of Evaporative Demand over China in CMIP5 Climate Models
Authors: Liu Wenbin , Sun Fubao 
Published: January 2017

Abstract
Atmospheric evaporative demand plays a pivotal role in global water and energy budgets, and its change is very important for drought monitoring, irrigation scheduling, and water resource management under a changing environment. Here, future changes of pan evaporation Epan, a measurable indicator for atmospheric evaporative demand, are first projected and attributed over China through a physically based approach, namely, the PenPan model, forced with outputs from 12 state-of-the-art climate models from phase 5 of the Coupled Model Intercomparison Project. An equidistant quantile mapping method was also used to correct the biases in GCMs outputs to reduce uncertainty in Epan projection. The results indicated that Epan would increase during the periods 2021–50 and 2071–2100 relative to the baseline period 1971–2000 under the representative concentration pathway (RCP) 4.5 and 8.5 scenarios, which can mainly be attributed to the projected increase in air temperature and vapor pressure deficit over China. The percentage increase of Epan is relatively larger in eastern China than in western China, which is due to the spatially inconsistent increases in air temperature, net radiation, wind speed, and vapor pressure deficit over China. The widely reported “pan evaporation paradox” was not well reproduced for the period 1961–2000 in the climate models, before or after bias correction, suggesting discrepancy between observed and modeled trends. With that caveat, it was found that the pan evaporation has been projected to increase at a rate of 117–167 mm yr−1 K−1 (72–80 mm yr−1 K−1) over China using the multiple GCMs under the RCP 4.5 (RCP 8.5) scenario with increased greenhouse gases and the associated warming of the climate system.