bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection
Authors: Avican Ummehan , Doruk Tugrul , Östberg Yngve , Fahlgren Anna , Forsberg Åke 
Published: January 2017

ABSTRACT

The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important human-pathogenic bacteria. Tat has been shown to be required for the virulence of
Yersinia pseudotuberculosis
, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in
in vivo
virulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a Δ
sufI
mutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization in
Y. pseudotuberculosis
.
In vivo
bioluminescent imaging of orally infected mice revealed that both the Δ
sufI
and Δ
tatC
mutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the Δ
tatC
mutant nor the Δ
sufI
mutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the Δ
tatC
and Δ
sufI
mutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the Δ
tatC
mutant.
Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice
Authors: Sullivan Joseph Pierce , Nair Nisha , Potula Hari-Hara , Gomes-Solecki Maria 
Published: January 2017

ABSTRACTLeptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H/HeJ mice withLeptospira interrogansserovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss andL. interrogansdissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. The infectious dose that led to consistent dissemination to kidney after conjunctival infection was ∼108leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified ∼105and ∼10 leptospires per μl of urine and per μg of kidney, respectively. Leptospira-specific IgM and IgG were detected at 15 days postinfection, and isotyping of the Ig subclass showed that the total IgG response switched from an IgG1 response to an IgG3 response after infection withL. interrogans. Histological periodic acid-Schiff D staining of infected kidney showed interstitial nephritis, mononuclear cell infiltrates, and reduced size of glomeruli. Quantification of proinflammatory immunomediators in kidney showed that keratinocyte-derived chemokine, macrophage inflammatory protein 2, RANTES, tumor necrosis factor alpha, gamma interferon, and interleukin-10 were upregulated in infected mice. We show that the kinetics of disease progression after infection via the ocular conjunctiva is delayed compared with infection via the standard intraperitoneal route. Differences may be related to the number ofL. interrogansspirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.
Genome-Wide Transcriptional Response to Varying RpoS Levels in Escherichia coli K-12
Authors: Wong Garrett T. , Bonocora Richard P. , Schep Alicia N. , Beeler Suzannah M. , Lee Fong Anna J. , Shull Lauren M. , Batachari Lakshmi E. , Dillon Moira , Evans Ciaran , Becker Carla J. , Bush Eliot C. , Hardin Johanna , Wade Joseph T. , Stoebel Daniel M. 
Published: January 2017

ABSTRACTThe alternative sigma factor RpoS is a central regulator of many stress responses inEscherichia coli. The level of functional RpoS differs depending on the stress. The effect of these differing concentrations of RpoS on global transcriptional responses remains unclear. We investigated the effect of RpoS concentration on the transcriptome during stationary phase in rich media. We found that 23% of genes in theE. coligenome are regulated by RpoS, and we identified many RpoS-transcribed genes and promoters. We observed three distinct classes of response to RpoS by genes in the regulon: genes whose expression changes linearly with increasing RpoS level, genes whose expression changes dramatically with the production of only a little RpoS (“sensitive” genes), and genes whose expression changes very little with the production of a little RpoS (“insensitive”). We show that sequences outside the core promoter region determine whether an RpoS-regulated gene is sensitive or insensitive. Moreover, we show that sensitive and insensitive genes are enriched for specific functional classes and that the sensitivity of a gene to RpoS corresponds to the timing of induction as cells enter stationary phase. Thus, promoter sensitivity to RpoS is a mechanism to coordinate specific cellular processes with growth phase and may also contribute to the diversity of stress responses directed by RpoS.IMPORTANCEThe sigma factor RpoS is a global regulator that controls the response to many stresses inEscherichia coli. Different stresses result in different levels of RpoS production, but the consequences of this variation are unknown. We describe how changing the level of RpoS does not influence all RpoS-regulated genes equally. The cause of this variation is likely the action of transcription factors that bind the promoters of the genes. We show that the sensitivity of a gene to RpoS levels explains the timing of expression as cells enter stationary phase and that genes with different RpoS sensitivities are enriched for specific functional groups. Thus, promoter sensitivity to RpoS is a mechanism that coordinates specific cellular processes in response to stresses.
ThiN as a Versatile Domain of Transcriptional Repressors and Catalytic Enzymes of Thiamine Biosynthesis
Authors: Hwang Sungmin , Cordova Bryan , Abdo Merna , Pfeiffer Friedhelm , Maupin-Furlow Julie A. 
Published: January 2017

ABSTRACT

Thiamine biosynthesis is commonly regulated by a riboswitch mechanism; however, the enzymatic steps and regulation of this pathway in archaea are poorly understood.
Haloferax volcanii
, one of the representative archaea, uses a eukaryote-like Thi4 (thiamine thiazole synthase) for the production of the thiazole ring and condenses this ring with a pyrimidine moiety synthesized by an apparent bacterium-like ThiC (2-methyl-4-amino-5-hydroxymethylpyrimidine [HMP] phosphate synthase) branch. Here we found that archaeal Thi4 and ThiC were encoded by leaderless transcripts, ruling out a riboswitch mechanism. Instead, a novel ThiR transcription factor that harbored an N-terminal helix-turn-helix (HTH) DNA binding domain and C-terminal ThiN (TMP synthase) domain was identified. In the presence of thiamine, ThiR was found to repress the expression of
thi4
and
thiC
by a DNA operator sequence that was conserved across archaeal phyla. Despite having a ThiN domain, ThiR was found to be catalytically inactive in compensating for the loss of ThiE (TMP synthase) function. In contrast, bifunctional ThiDN, in which the ThiN domain is fused to an N-terminal ThiD (HMP/HMP phosphate [HMP-P] kinase) domain, was found to be interchangeable for ThiE function and, thus, active in thiamine biosynthesis. A conserved Met residue of an extended α-helix near the active-site His of the ThiN domain was found to be important for ThiDN catalytic activity, whereas the corresponding Met residue was absent and the α-helix was shorter in ThiR homologs. Thus, we provide new insight into residues that distinguish catalytic from noncatalytic ThiN domains and reveal that thiamine biosynthesis in archaea is regulated by a transcriptional repressor, ThiR, and not by a riboswitch.

IMPORTANCE
Thiamine pyrophosphate (TPP) is a cofactor needed for the enzymatic activity of many cellular processes, including central metabolism. In archaea, thiamine biosynthesis is an apparent chimera of eukaryote- and bacterium-type pathways that is not well defined at the level of enzymatic steps or regulatory mechanisms. Here we find that ThiN is a versatile domain of transcriptional repressors and catalytic enzymes of thiamine biosynthesis in archaea. Our study provides new insight into residues that distinguish catalytic from noncatalytic ThiN domains and reveals that archaeal thiamine biosynthesis is regulated by a ThiN domain transcriptional repressor, ThiR, and not by a riboswitch.
CO2 diffusion into pore spaces limits weathering rate of an experimental basalt landscape
Authors: van Haren Joost , Dontsova Katerina , Barron-Gafford Greg A. , Troch Peter A. , Chorover Jon , Delong Stephen B. , Breshears David D. , Huxman Travis E. , Pelletier Jon D. , Saleska Scott R. , Zeng Xubin , Ruiz Joaquin 
Published: January 2017

Abstract
Basalt weathering is a key control over the global carbon cycle, though in situ measurements of carbon cycling are lacking. In an experimental, vegetation-free hillslope containing 330 m3 of ground basalt scoria, we measured real-time inorganic carbon dynamics within the porous media and seepage flow. The hillslope carbon flux (0.6–5.1 mg C m–2 h–1) matched weathering rates of natural basalt landscapes (0.4–8.8 mg C m–2 h–1) despite lacking the expected field-based impediments to weathering. After rainfall, a decrease in CO2 concentration ([CO2]) in pore spaces into solution suggested rapid carbon sequestration but slow reactant supply. Persistent low soil [CO2] implied that diffusion limited CO2 supply, while when sufficiently dry, reaction product concentrations limited further weathering. Strong influence of diffusion could cause spatial heterogeneity of weathering even in natural settings, implying that modeling studies need to include variable soil [CO2] to improve carbon cycling estimates associated with potential carbon sequestration methods.
The control of the tropical North Atlantic on Holocene millennial climate oscillations
Authors: Domínguez-Villar David , Wang Xianfeng , Krklec Kristina , Cheng Hai , Edwards R. Lawrence 
Published: January 2017

Abstract
Changes in ocean dynamics in the northern North Atlantic affect the thermohaline circulation that controls global climate. During glacial and deglaciation periods these dynamics are enhanced due to large variations in the surface ocean density caused by changes in glacier volumes. During full interglacial conditions, the dominant role of the northern North Atlantic on global climate is limited due to the reduced discharge of freshwater to the ocean, causing other regional dynamics to gain importance. Here we present a speleothem δ18O record from the Iberian Peninsula that supports that the northern North Atlantic and tropical North Atlantic were both source regions of millennial climate oscillations during the Holocene. The speleothem δ18O signal records millennial time-scale changes in the hydrological cycle as a result of persistent anomalies of the Gulf Stream–North Atlantic Current dynamics. In addition, the speleothem δ18O record shows synchronous variability with records from the eastern Pacific region though the entire Holocene, whereas records from western Pacific region have limited or no correlation beyond periods of major instability of the northern North Atlantic. The discontinuous climate connection among the studied records is the result of different mechanisms affecting the climate system that originated in distant regions. We suggest that two regions, the tropical North Atlantic and northern North Atlantic, alternate their dominance as source regions causing millennial climate anomalies in large planetary regions. The duration of these persistent climate changes and the extension of the regions affected depend on the region triggering the anomaly because different mechanisms affecting the climate system are involved.
Block-controlled hillslope form and persistence of topography in rocky landscapes
Authors: Glade Rachel C. , Anderson Robert S. , Tucker Gregory E. 
Published: January 2017

Abstract
Rocky hillslopes dotted with boulder-sized blocks and covered by a thin, nonuniform soil are common in both steep landscapes and arid environments on Earth, as well as on other planets. While the evolution of soil-mantled, convex-upward hillslopes in uniform lithology is reasonably well understood, the influence of heterogeneous lithology and geologic structure on hillslope form and evolution has yet to be properly addressed. Landscapes developed in layered sedimentary rocks feature sharp-edged landforms such as mesas and hogbacks that exhibit steep, linear to concave-upward ramps with scattered blocks calved from resistant rock layers overlying softer strata. Here we show that blocks can control the persistence of topography and the form and evolution of hillslopes in these landscapes. We present a numerical model demonstrating that incorporation of feedbacks between block release, interruption of soil creep by blocks, and sporadic downslope movement of blocks are necessary and sufficient to capture the morphology and evolution of these landscapes. Numerical results are reproduced by a simple analytical solution that predicts steady-state concave hillslope form and average slope angle from block size and spacing. Our results illuminate previously unrecognized hillslope feedbacks, advancing our understanding of the geomorphology of rocky hillslopes. On a landscape scale, our findings establish a quantitative method to address the migration of sharp edges and the persistence of topography in layered landscapes.
Location, location, location: The variable lifespan of the Laramide orogeny
Authors: Copeland Peter , Currie Claire A. , Lawton Timothy F. , Murphy Michael A. 
Published: January 2017

Abstract
The Laramide orogeny had a spatially variable lifespan, which we explain using a geodynamic model that incorporates onset and demise of flat-slab subduction. Laramide shortening and attendant uplift began in southeast California (USA) at ca. 90 Ma, swept to the northeast to arrive in the Black Hills of South Dakota (USA) at ca. 60 Ma, and concluded in South Dakota within ∼10 m.y. During subsequent slab rollback, the areal extent of Laramide deformation decreased as the eastern edge of active deformation retreated to the southwest rapidly from ca. 55 to 45 Ma and more slowly from ca. 45 to 40 Ma, with deformation ultimately ceasing in the southwestern part of the orogen at ca. 30 Ma. Geodynamic modeling of this process suggests that changes in the strength of the North America plate and densification of the Farallon plate played important roles in controlling the areal extent of the Laramide orogen and hence the lifespan of the orogenic event at any particular location in western North America.
Controls and feedbacks in the coupling of mountain channels and hillslopes
Authors: Golly Antonius , Turowski Jens M. , Badoux Alexandre , Hovius Niels 
Published: January 2017

Abstract
Mountain channels can be strongly coupled with adjacent hillslopes, exchanging both mass and energy. However, hypotheses of the underlying cause and effect relations are based on indirect observations that do not resolve the mechanics of channel-hillslope coupling at the process scale. Here we present direct observational data of a coupled channel-hillslope system in the catchment area of the Erlenbach, a mountain stream in Switzerland. A slow-moving landslide flanking this alpine stream failed after a flood had eroded an alluvial step in the channel at its base, representing evidence for an upsystem link in channel-hillslope coupling. Progressive accumulation of landslide debris in the channel resulted in a renewed step, stabilizing the hillslope and restoring the channel step in a downsystem link. Thus, upsystem and downsystem coupling mechanisms are joined in a negative feedback cycle. In this cycle, debuttressing and rebuttressing due to channel bed erosion and alluviation are the dominant controls on hillslope stability. Based on an order of magnitude estimate it is plausible that the observed feedback mechanism is a relevant process in the production of coarse (&gt;2 mm) sediment in the Erlenbach.
Myocardial infarction in the Wisconsin Longitudinal Study: the interaction among environmental, health, social, behavioural and genetic factors
Authors: Gonzales Tina K , Yonker James A , Chang Vicky , Roan Carol L , Herd Pamela , Atwood Craig S 
Published: January 2017

ObjectivesThis study examined how environmental, health, social, behavioural and genetic factors interact to contribute to myocardial infarction (MI) risk.DesignSurvey data collected by Wisconsin Longitudinal Study (WLS), USA, from 1957 to 2011, including 235 environmental, health, social and behavioural factors, and 77 single- nucleotide polymorphisms were analysed for association with MI. To identify associations with MI we utilized recursive partitioning and random forest prior to logistic regression and chi-squared analyses.Participants6198 WLS participants (2938 men; 3260 women) who (1) had a MI before 72 years and (2) had a MI between 65 and 72 years.ResultsIn men, stroke (LR OR: 5.01, 95% CI 3.36 to 7.48), high cholesterol (3.29, 2.59 to 4.18), diabetes (3.24, 2.53 to 4.15) and high blood pressure (2.39, 1.92 to 2.96) were significantly associated with MI up to 72 years of age. For those with high cholesterol, the interaction of smoking and lower alcohol consumption increased prevalence from 23% to 41%, with exposure to dangerous working conditions, a factor not previously linked with MI, further increasing prevalence to 50%. Conversely, MI was reported in <2.5% of men with normal cholesterol and no history of diabetes or depression. Only stroke (4.08, 2.17 to 7.65) and diabetes (2.71, 1.81 to 4.04) by 65 remained significantly associated with MI for men after age 65. For women, diabetes (5.62, 4.08 to 7.75), high blood pressure (3.21, 2.34 to 4.39), high cholesterol (2.03, 1.38 to 3.00) and dissatisfaction with their financial situation (4.00, 1.94 to 8.27) were significantly associated with MI up to 72 years of age. Conversely, often engaging in physical activity alone (0.53, 0.32 to 0.89) or with others (0.34, 0.21 to 0.57) was associated with the largest reduction in odds of MI. Being non-diabetic with normal blood pressure and engaging in physical activity often lowered prevalence of MI to 0.2%. Only diabetes by 65 (4.25, 2.50 to 7.24) and being exposed to dangerous work conditions at 54 (2.24, 1.36 to 3.69) remained significantly associated with MI for women after age 65, while still menstruating at 54 (0.46, 0.23 to 0.91) was associated with reduced odds of MI.ConclusionsTogether these results indicate important differences in factors associated with MI between the sexes, that combinations of factors greatly influence the likelihood of MI, that MI-associated factors change and associations weaken after 65 years of age in both sexes, and that the limited genotypes assessed were secondary to environmental, health, social and behavioral factors.
Cohort study investigating the effects of first stage of the English tobacco point-of-sale display ban on awareness, susceptibility and smoking uptake among adolescents
Authors: Bogdanovica Ilze , McNeill Ann , Britton John 
Published: January 2017

ObjectiveA prospective evaluation of the effect of 2012 point-of-sale (PoS) display ban in supermarkets in England on perceived exposure to PoS displays, and on changes in susceptibility and smoking uptake among young people.DesignCohort study.SettingsSeven schools in Nottinghamshire, England.Participants1035 11–16-year-old school children.Primary and secondary outcome measuresChanges in reported exposure to PoS displays before and after prohibition, and the association between exposure to and awareness of PoS displays and change in susceptibility to smoking and smoking status between 2011 and 2012 (before the ban) and 2012 and 2013 (after the ban).ResultsThe proportion of children noticing tobacco PoS displays in supermarkets most or every time they visited a shop changed little between 2011 and 2012 (59.6% (95% CI 56.6% to 62.6%) and 58.8% (95% CI 55.8% to 61.8%), respectively); but decreased by about 13 percentage points to 45.7% (95% CI 42.7% to 48.7%) in 2013, after the ban. However, after adjusting for confounders, implementation of the first stage of the PoS ban in 2012 did not result in significant changes in the relation between susceptibility to smoking and smoking status and exposure to and awareness of PoS displays.ConclusionsProhibition of PoS in large supermarkets resulted in a decline in the proportion of young people noticing PoS displays in large shops, but little or no change in smoking uptake or susceptibility. It remains to be seen whether extension of the PoS ban to all shops in 2015 has a more marked effect.
Capacity of English NHS hospitals to monitor quality in infection prevention and control using a new European framework: a multilevel qualitative analysis
Authors: Iwami Michiyo , Ahmad Raheelah , Castro-Sánchez Enrique , Birgand Gabriel , Johnson Alan P , Holmes Alison 
Published: January 2017

Objective(1) To assess the extent to which current English national regulations/policies/guidelines and local hospital practices align with indicators suggested by a European review of effective strategies for infection prevention and control (IPC); (2) to examine the capacity of local hospitals to report on the indicators and current use of data to inform IPC management and practice.DesignA national and local-level analysis of the 27 indicators was conducted. At the national level, documentary review of regulations/policies/guidelines was conducted. At the local level data collection comprised: (a) review of documentary sources from 14 hospitals, to determine the capacity to report performance against these indicators; (b) qualitative interviews with 3 senior managers from 5 hospitals and direct observation of hospital wards to find out if these indicators are used to improve IPC management and practice.Setting2 acute English National Health Service (NHS) trusts and 1 NHS foundation trust (14 hospitals).Participants3 senior managers from 5 hospitals for qualitative interviews.Primary and secondary outcome measuresAs primary outcome measures, a ‘Red-Amber-Green’ (RAG) rating was developed reflecting how well the indicators were included in national documents or their availability at the local organisational level. The current use of the indicators to inform IPC management and practice was also assessed. The main secondary outcome measure is any inconsistency between national and local RAG rating results.ResultsNational regulations/policies/guidelines largely cover the suggested European indicators. The ability of individual hospitals to report some of the indicators at ward level varies across staff groups, which may mask required improvements. A reactive use of staffing-related indicators was observed rather than the suggested prospective strategic approach for IPC management.ConclusionsFor effective patient safety and infection prevention in English hospitals, routine and proactive approaches need to be developed. Our approach to evaluation can be extended to other country settings.