bluuebunny/crossref_metadata_2025 huggingface dataset:
Metatranscriptomic Evidence for Co-Occurring Top-Down and Bottom-Up Controls on Toxic Cyanobacterial Communities
Authors: Steffen Morgan M. , Belisle B. Shafer , Watson Sue B. , Boyer Gregory L. , Bourbonniere Richard A. , Wilhelm Steven W.
Published: February 2015

Little is known about the molecular and physiological function of co-occurring microbes within freshwater cyanobacterial harmful algal blooms (cHABs). To address this, community metatranscriptomes collected from the western basin of Lake Erie during August 2012 were examined. Using sequence data, we tested the hypothesis that the activity of the microbial community members is independent of community structure. Predicted metabolic and physiological functional profiles from spatially distinct metatranscriptomes were determined to be ≥90% similar between sites. Targeted analysis of
Microcystis aeruginosa
, the historical causative agent of cyanobacterial harmful algal blooms over the past ∼20 years, as well as analysis of
Planktothrix agardhii
and
Anabaena cylindrica
, revealed ongoing transcription of genes involved in microcystin toxin synthesis as well as the acquisition of both nitrogen and phosphorus, nutrients often implicated as independent bottom-up drivers of eutrophication in aquatic systems. Transcription of genes involved in carbon dioxide (CO
2
) concentration and metabolism also provided support for the alternate hypothesis that high-pH conditions and dense algal biomass result in CO
2
-limiting conditions that further favor cyanobacterial dominance. Additionally, the presence of
Microcystis
-specific cyanophage sequences provided preliminary evidence of possible top-down virus-mediated control of cHAB populations. Overall, these data provide insight into the complex series of constraints associated with
Microcystis
blooms that dominate the western basin of Lake Erie during summer months, demonstrating that multiple environmental factors work to shape the microbial community.
Host Erythrocyte Environment Influences the Localization of Exported Protein 2, an Essential Component of the Plasmodium Translocon
Authors: Meibalan Elamaran , Comunale Mary Ann , Lopez Ana M. , Bergman Lawrence W. , Mehta Anand , Vaidya Akhil B. , Burns James M.
Published: February 2015

Malaria parasites replicating inside red blood cells (RBCs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. PTEX, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (PVM) in
Plasmodium falciparum
-infected erythrocytes. Proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as Maurer's clefts, small vesicles, and a tubovesicular network. Comparable studies of protein trafficking in
Plasmodium vivax
-infected reticulocytes are limited. With
Plasmodium yoelii
-infected reticulocytes, we identified exported protein 2 (Exp2) in a proteomic screen of proteins putatively transported across the PVM. Immunofluorescence studies showed that
P. yoelii
Exp2 (
Py
Exp2) was primarily localized to the PVM. Unexpectedly,
Py
Exp2 was also associated with distinct, membrane-bound vesicles in the reticulocyte cytoplasm. This is in contrast to
P. falciparum
in mature RBCs, where
P. falciparum
Exp2 (
Pf
Exp2) is exclusively localized to the PVM. Two
P. yoelii
-exported proteins, PY04481 (encoded by a
pyst-a
gene) and PY06203 (
Py
pAg-1), partially colocalized with these
Py
Exp2-positive vesicles. Further analysis revealed that with
P. yoelii
,
Plasmodium berghei
, and
P. falciparum
, cytoplasmic Exp2-positive vesicles were primarily observed in CD71
+
reticulocytes versus mature RBCs. In transgenic
P. yoelii
17X parasites, the association of hemagglutinin-tagged
Py
Exp2 with the PVM and cytoplasmic vesicles was retained, but the
pyexp2
gene was refractory to deletion. These data suggest that the localization of Exp2 in mouse and human RBCs can be influenced by the host cell environment. Exp2 may function at multiple points in the pathway by which parasites traffic proteins into and through the reticulocyte cytoplasm.
Pretreatment lymphocyte–monocyte ratio as a potential prognostic factor in a cohort of patients with upper tract urothelial carcinoma
Authors: Hutterer Georg C , Sobolev N , Ehrlich Georg C , Gutschi Thomas , Stojakovic Tatjana , Mannweiler Sebastian , Pummer Karl , Zigeuner Richard , Pichler Martin , Dalpiaz Orietta
Published: February 2015

Aims

To investigate the potential prognostic impact of the lymphocyte–monocyte ratio (LMR) in a large European cohort of patients with localised upper urinary tract urothelial carcinoma (UTUC). The LMR as an indicator of systemic inflammatory response has been shown to represent a potential prognostic factor in various types of human cancers. Up to date, the prognostic significance of the LMR in UTUC has not been evaluated.

Methods

Clinico-pathological data from 182 non-metastatic patients with UTUC, operated between 1990 and 2012 at a single tertiary academic centre, were evaluated retrospectively. Pretreatment LMR was assessed 1 day before surgery. Patients were categorised using an LMR cut-off value of 2.0 according to a calculation by receiver-operating curve analysis. Patients’ overall survival (OS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the LMR, a multivariate proportional Cox regression model was applied for OS.

Results

In multivariate analyses, age on the date of surgery (<65 vs ≥65 years, HR=2.10, 95% CI 1.22 to 3.64), pathological T-stage (pT1 vs pT2–4, HR=2.15, 95% CI 1.26 to 3.67), as well as the LMR (<2 vs ≥2, HR=0.56, 95% CI 0.35 to 0.92) were independent predictors of OS of patients with UTUC.

Conclusions

In the cohort studied, patients with an elevated (≥2) preoperative LMR had a subsequently longer OS after radical surgery for UTUC, compared with those with a low (<2) preoperative LMR. Thus, we believe this parameter might be considered an additional prognostic factor in UTUC in the future.
Underuse of an invasive strategy for patients with diabetes with acute coronary syndrome: a nationwide study
Authors: Gustafsson Ida , Hvelplund Anders , Hansen Kim Wadt , Galatius Søren , Madsen Mette , Jensen Jan Skov , Tilsted Hans-Henrik , Terkelsen Christian Juhl , Jensen Lisette Okkels , Jørgensen Erik , Madsen Jan Kyst , Abildstrøm Steen Zabell
Published: February 2015

Background

Guidelines recommend an early invasive strategy for patients with diabetes with acute coronary syndromes (ACS). We investigated if patients with diabetes with ACS are offered coronary angiography (CAG) and revascularisation to the same extent as patients without diabetes.

Methods and results

The study is a nationwide cohort study linking Danish national registries containing information on healthcare. The study population comprises all patients hospitalised with first-time ACS in Denmark during 2005–2007 (N=24 952). Diabetes was defined as claiming of a prescription for insulin and/or oral hypoglycaemic agents within 6 months prior to the ACS event. Diabetes was present in 2813 (11%) patients. Compared with patients without diabetes, patients with diabetes were older (mean 69 vs 67 years, p<0.0001), less often males (60% vs 64%, p=0.0001) and had more comorbidity. Fewer patients with diabetes underwent CAG: cumulative incidence 64% vs 74% for patients without diabetes, HR=0.72 (95% CI 0.69 to 0.76, p<0.0001); adjusted for age, sex, previous revascularisation and comorbidity HR=0.78 (95% CI 0.74 to 0.82, p<0.0001). More patients with diabetes had CAG showing two-vessel or three-vessel disease (53% vs 38%, p<0.0001). However, revascularisation after CAG revealing multivessel disease was less likely in patients with diabetes (multivariable adjusted HR=0.76, 95% CI 0.68 to 0.85, p<0.0001).

Conclusions

In this nationwide cohort of patients with incident ACS, patients with diabetes were found to be less aggressively managed by an invasive treatment strategy. The factors underlying the decision to defer an invasive strategy in patients with diabetes are unclear and merit further investigation.
Evaluation and management of hypersensitivity reactions to chemotherapy agents
Authors: Tham Elizabeth Huiwen , Cheng Yew Kuang , Tay Miah Hiang , Alcasabas Ana Patricia , Shek Lynette Pei-Chi
Published: February 2015

Hypersensitivity reactions to chemotherapy drugs pose significant difficulties in management, especially when no suitable alternative is available or acceptable and delay in continuation of treatment may be life-threatening. Such reactions may be IgE- or non-IgE-mediated and have varied manifestations. Timely recognition and treatment of life-threatening hypersensitivity reactions are essential. Identification of patients at high risk of developing hypersensitivity reactions allows risk stratification to guide clinical decision-making. Skin testing for carboplatin hypersensitivity has good predictive value but is not yet established for oxaliplatin and taxane hypersensitivity. Rapid desensitisation may be considered if no suitable alternative drug is available. Available protocols have shown good safety and efficacy but must be performed in an appropriate setting with adequate monitoring. There are many avenues for research into the utility of skin testing for other chemotherapy agents as well as in vitro tests.
A pedigree‐based genetic appraisal of Boxer ARVC and the role of the Striatin mutation
Authors: Cattanach B. M. , Dukes‐McEwan J. , Wotton P. R. , Stephenson H. M. , Hamilton R. M.
Published: February 2015

The objective of this paper was to investigate by pedigree‐based genetic means the origins and inheritance of arrhythmogenic right ventricular cardiomyopathy (ARVC) in UK Boxers and assess the role of the proposed causal mutation in the gene, Striatin (STRN). All ARVC cases traced back to a small number of imported American dogs deriving from the group of Boxers studied by Harpster (1983) to define the disease, strongly suggesting that the disease is the same in the two countries. Dogs with and without the STRN mutation were found in both ARVC affected and normal Boxers showing that the mutation is not responsible for the disease. Evidence was found that the STRN mutation is, however, genetically linked with the gene responsible on the same chromosome. The linkage implies that the two genes can separate by meiotic recombination such that both ARVC‐affected and ARVC‐unaffected lines of dogs may carry either the STRN mutation or its wild‐type allele. These have been found. Homozygotes for the STRN mutation tended to be severely affected at early ages, suggesting that there is an interaction between the known effects of the STRN mutation on the cardiomyocyte and ARVC.
Stratigraphic relations of Santorini’s intracaldera fill and implications for the rate of post-caldera volcanism
Authors: Johnston E. N. , Sparks R. S. J. , Nomikou P. , Livanos I. , Carey S. , Phillips J. C. , Sigurdsson H.
Published: February 2015

We propose a new volcanological interpretation of Santorini’s intracaldera fill deposits as revealed by seismic reflection profiles. This interpretation, along with supplementary gravity and geophysical studies, reveals three distinct volcaniclastic units (1–3). From top to bottom these units are attributed to (1) modern infilling sediment, (2) shallow marine phreatomagmatic volcanism associated with the relatively recent formation of the Kameni Islands, and (3) downfaulted ‘Minoan’ pyroclastic deposits, which formed during caldera collapse towards the end of the Bronze Age eruption. Estimates of the volumes of the seismic units and Kameni Islands yield a dense rock equivalent magma volume of 4.85 ± 0.7 km
3
. The average rate of volcanism over the past
c
. 3641 years is estimated at 1.3 ×10
−3
 km
3
 a
−1
, and is similar to the rate since the AD 1707 eruption of 1.2 ×10
−3
 km
3
 a
−1
based on historical lava volume estimates.
Tectono-sedimentary evolution of the Permian–Triassic extension event in the Zagros basin (Iran): results from analogue modelling
Authors: Madani-Kivi Mehrdad , Zulauf Gernold
Published: February 2015

Since the 1970s, the largest oil and gas reservoirs have been discovered in the Permian–Early Triassic formations in Saudi Arabia. Thus, this time period is important for the discovery of new oil reserves in Iran. The Arabian passive continental margin has undergone lithospheric extension during the Permian–Triassic, which led to the formation of the Neo-Tethys. The aim of this paper is to describe the development of the continental rift basin in the Zagros region based on the tectono-sedimentological evolution. We have studied well-log data to specify the distribution of synrift deposits in the Zagros and have related this information to the modelling. Environmental changes indicated by various sedimentary sequences, from a siliciclastic basin to a carbonate platform setting, are described. The Cambrian Hormuz salt, which overlies the metamorphosed Precambrian basement, becomes effective as a basal detachment layer influencing the style of overburden deformation during the Permian–Triassic extension event. We have investigated the formation of various structures linked to the presence or absence of the Hormuz layer by analogue modelling and relating these structures to the Late Palaeozoic sedimentation. Based on results of the analogue modelling, we argue that the basal detachment layer (Hormuz series) has contributed to the various structural styles of the extensional basin development in the Fars domain and the Lorestan domain.
Latitudinal variations in submarine channel sedimentation patterns: the role of Coriolis forces
Authors: Cossu R. , Wells M. G. , Peakall J.
Published: February 2015

Turbidity currents transport clastic sediments from the continental margin to deep ocean basins and along their pathways they erode large submarine channels. The driving mechanisms for submarine channel evolution are highly complex, reflected by recent debates about the formation and global distribution of sinuosity in turbidite channels. We present novel experiments on channelized gravity currents running over an erodible bed, where the magnitude of Coriolis forces is changed to reproduce conditions at low and high latitudes. We find a striking systematic change in deposition and erosion patterns as Coriolis forces become dominant at high latitudes so that erosion and deposition occur only on opposite sides of channels; in contrast, at low latitudes significant inner-bank intra-channel bars form on alternate sides of sinuous channels. Our observations show very good agreement with sedimentation patterns in Coriolis-dominated contourite drift systems and with deposits in modern and ancient turbidity current channels. We hypothesize that Coriolis forces are a key parameter for submarine channel evolution and sedimentary architecture at high latitudes but not at low latitudes; this proposal offers a new approach to interpret deep-sea architectural features at high latitudes.
Mesozoic and Cenozoic deformations in the Raggyorcaka area, Tibet: implications for the tectonic evolution of the North Qiangtang terrane
Authors: Liang Xiao , Wang Genhou , Yuan Guo-Li , Che Xiaochao
Published: February 2015

The Mesozoic and Cenozoic deformations of the North Qiangtang terrane reflect a portion of the collisional tectonics of the Tethys Ocean, involving Late Triassic, Early Cretaceous and Cenozoic intraplate structures of shallow to superficial tectonic levels. The structural mapping of the Permian–Triassic structural layer indicates that the Mesozoic structural style is dominated by Early Cretaceous horizontal contractional deformations characterized by NW–SE-trending thrust faults and flexural-slip folds. These folds and thrusts were superimposed on Late Triassic buckle folds. Structural analysis of deformations of the Neogene and Quaternary sedimentary layers indicates that there was an obvious transition in the Cenozoic tectonic evolution of the North Qiangtang terrane, which can be divided into two deformation stages. In episode I (50–40 to 18 Ma), the crust experienced large-scale north–south horizontal shortening and vertical thickening shown by buckle folds and thrust faults. In episode II (18 Ma–present day), east–west passive extension formed conjugate strike-slip fault systems and pull-apart basins. During episode II, the Qiangtang basin was extruded eastwards, and a number of superficial north–south-trending buckle folds were formed.

Supplementary material:

Supplementary material is available at
http://www.geolsoc.org.uk/SUP18787
.
Dynamic weakening along incipient low-angle normal faults in pelagic limestones (Southern Apennines, Italy)
Authors: Novellino Rocco , Prosser Giacomo , Spiess Richard , Viti Cecilia , Agosta Fabrizio , Tavarnelli Enrico , Bucci Francesco
Published: February 2015

Slip along low-angle normal faults is a mechanical paradox requiring activation of strain weakening mechanisms. Microstructures present in the slip zones of incipient low-angle normal faults cutting carbonates in the Southern Apennines of Italy show that slip was promoted by two weakening mechanisms producing a reduction of the friction coefficient: (1) high pore fluid pressures; (2) dynamic weakening related to thermal decomposition indicated by decarbonation microstructures and concomitant localized dynamic calcite recrystallization. Furthermore, as a consequence of thermal decomposition, nanoparticles occur as infilling of injection veins, suggesting that powder lubrication processes are active along the slip surface during seismic slip.

Supplementary materials:

A geological sketch of the study area, detailed field photographs of the studied faults and detailed micrographs are available at
http://www.geolsoc.org.uk/SUP18806
.
An inclined Vulcanian explosion and associated products
Authors: Cole P. D. , Stinton A. J. , Odbert H. M. , Bonadonna C. , Stewart R. C.
Published: February 2015

Vulcanian explosions generate some of the most hazardous types of volcanic phenomena, including pyroclastic density currents. Non-vertical directionality of an explosion promotes asymmetrical distribution of proximal hazards around the volcano. Although critical, such behaviour is relatively uncommon and has been seldom documented. Here we present, for the first time, evidence both from geophysical monitoring and field survey data that records the occurrence of such an event. Thermal imagery captures a Vulcanian explosion at Soufrière Hills Volcano, Montserrat, which occurred during a large partial lava dome collapse in February 2010, and was inclined at about 25° from the vertical in a northerly direction. Pyroclastic products were preferentially distributed to the north and included: an unusual pumice boulder deposit that we propose was formed by a dilute pyroclastic density current; pumice flow deposits; and a proximal lapilli and block fallout lobe. The inclined nature of the explosion is attributed to the asymmetric geometry around the vent. The explosion-derived pyroclastic density currents had notably lower velocities than those associated with lateral blasts, which, we suggest, result from a separate and distinct mechanism. These inclined explosions present an additional mechanism that is able to generate directed pyroclastic density currents, with consequent implications for hazard assessment.
Rifting and mafic magmatism in the Hebridean basins
Authors: Hole M. J. , Millett J. M. , Rogers N. W. , Jolley D. W.
Published: February 2015

Basalt dykes from the regional dyke swarm of the British Palaeogene Igneous Province (BPIP) were emplaced parallel to structural lineaments linking onshore and offshore volcanic edifices. Basalts that underwent minimal interaction with the crust have Mg# 60–75, εNd
58
c
. 8,
206
Pb/
204
Pb
c
. 17.5, δ
18
O 5.9 ± 0.3‰, and
87
Sr/
86
Sr <0.7040. Basalts with convex-upwards REE profiles ([La/Sm]
N
<1; [Sm/Yb]
N
>1) were generated by limited extents of melting (<10%) in the garnet–spinel transition of the upper mantle. Basalts with LREE-depleted ([La/Sm]
N
<1) or flat REE profiles require substantial (up to 20%) melting of spinel lherzolite. Modelling of major element compositions and olivine equilibration temperatures indicates that the mantle potential temperature was a maximum of 1530 °C beneath the BPIP at 58–60 Ma. Magmatism occurred at the periphery of a mantle thermal anomaly (proto-Iceland plume;
T
P
≤ 1560 °C) centred beneath western Greenland. The distribution of BPIP magmas was controlled by extensional tectonism driven by plate boundary forces resulting from plate reorganizations in the northern hemisphere starting at
c
. 62 Ma. The well-known mildly alkaline lava piles of Skye and Mull represent volcanoes on the flanks of the resulting rift system.
Sedimentology and magnetic susceptibility of recent sediments from New Caledonia
Authors: Jadot Hélène , Boulvain Frédéric
Published: February 2015

The interpretation of the primary origin of the minerals carrying the magnetic susceptibility (MS) signal from ancient rocks suffers notably from the scarcity of studies on Recent sediments. To bring new data, a study of tropical coastal sediments of New Caledonia was undertaken. This island is surrounded by a nearly uninterrupted reef barrier, isolating a wide lagoon from the open ocean. The erosion of extremely varied rocks (from mantle rocks to laterites) produces different types of detrital sediments, which are mixed with the indigenous precipitated carbonates. This generates different types of coastal sediments, detrital- or carbonate-dominated or mixed. More than 300 samples were analysed for grain size, nature of sediment, MS and geochemistry (major elements). The first results show that: (a) carbonate sands and carbonate silts are characterized by lower MS than detrital sediments; (b) the MS signal of mixed sediments is mostly influenced by the proportion of detrital sediments; (c) MS is directly correlated with Mn and Fe content; (d) beachrocks are characterized by lower MS than equivalent loose sediment; (e) the MS signal of carbonate sediments is locally positively correlated with granulometry; (f) there is no MS change between surface and 20 cm deep samples; and (g) when the subsurface sediment is reducing, the MS is higher than that from surface sediment.
Forcing factors of the magnetic susceptibility signal in lagoonal and subtidal depositional cycles from the Zachełmie section (Eifelian, Holy Cross Mountains, Poland)
Authors: Grabowski J. , Narkiewicz M. , De Vleeschouwer D.
Published: February 2015

Eifelian dolomites in the Zachełmie Quarry exhibit metre-scale depositional cyclicity, both in the lower, lagoonal part of the section and in the upper, shallow subtidal portion. Magnetic properties were studied in 30 samples (at
c.
1 m intervals), including magnetic susceptibility (MS) and anhysteretic and isothermal remanent magnetization. The rock magnetic parameters are compared with the results of thin-section study and elemental chemistry. The forcing factors driving the MS pattern are identified. The MS signal is mostly related to a finely dispersed hematite, controlled by terrigenous input. Magnetite plays a subordinate role and it is confined to less terrigenous horizons relatively enriched in uranium and phosphorus. Results of high-resolution (
c.
8 cm intervals) MS field measurements show a good correlation with depositional shallowing-upwards cycles, especially in the lagoonal part of the section, where variations of rock magnetic properties and geochemical (redox and productivity) indices are very small. High MS values occur in the bottom part of the cycles and they decrease upwards. Time-series analyses of the MS signal reveal the dominance of
c.
1.7 m cycles, grouped into
c.
10 m bundles. The former cycles probably reflect precession-driven changes in monsoonal intensity, whereas the latter may have been controlled by 100 kyr eccentricity.
Tectonic and magmatic segmentation of the Global Ocean Ridge System: a synthesis of observations
Authors: Carbotte Suzanne M. , Smith Deborah K. , Cannat Mathilde , Klein Emily M.
Published: February 2015

Mid-ocean ridges display tectonic segmentation defined by discontinuities of the axial zone, and geophysical and geochemical observations suggest segmentation of the underlying magmatic plumbing system. Here, observations of tectonic and magmatic segmentation at ridges spreading from fast to ultraslow rates are reviewed in light of influential concepts of ridge segmentation, including the notion of hierarchical segmentation, spreading cells and centralized v. multiple supply of mantle melts. The observations support the concept of quasi-regularly spaced principal magmatic segments, which are 30–50 km long on average at fast- to slow-spreading ridges and fed by melt accumulations in the shallow asthenosphere. Changes in ridge properties approaching or crossing transform faults are often comparable with those observed at smaller offsets, and even very small discontinuities can be major boundaries in ridge properties. Thus, hierarchical segmentation models that suggest large-scale transform fault-bounded segmentation arises from deeper level processes in the asthenosphere than the finer-scale segmentation are not generally supported. The boundaries between some but not all principal magmatic segments defined by ridge axis geophysical properties coincide with geochemical boundaries reflecting changes in source composition or melting processes. Where geochemical boundaries occur, they can coincide with discontinuities of a wide range of scales.
A method for characterizing basement rocks from borehole images
Authors: Murray Ann
Published: February 2015

Basement rocks tend to have negligible primary (rock matrix) porosity and, where present, almost all porosity is fracture-related. An insight into fracture type and distribution is therefore of importance when attempting to predict potential flow zones in hydrocarbon reservoirs. In the absence of core, borehole images provide a proven means of characterizing fractures within basement rocks. This paper will concentrate upon the classification and characterization of basement structural elements, including fractures, faults and breccias, versus lithological elements, such as foliations and intrusion boundaries from borehole images. In addition, suggestions of how to differentiate present-day
in-situ
stress indicators from natural fractures will be made as these features may provide important information regarding open fracture set orientations. Examples of microresistivity and acoustic borehole images acquired in fractured igneous basement rocks from oil wells in Yemen will be presented together with a suggested methodology for their interpretation. The discussion will be based on hydrocarbon reservoirs; however, the methodology outlined can potentially have wider applications in, for example, groundwater pollution prevention schemes or groundwater extraction, radioactive waste disposal, geothermal energy resources and deep-drilling research programmes.
Aquaporin-1 facilitates pressure-driven water flow across the aortic endothelium
Authors: Nguyen Tieuvi , Toussaint Jimmy , Xue Yan , Raval Chirag , Cancel Limary , Russell Stewart , Shou Yixin , Sedes Omer , Sun Yu , Yakobov Roman , Tarbell John M. , Jan Kung-ming , Rumschitzki David S.
Published: February 2015

Aquaporin-1, a ubiquitous water channel membrane protein, is a major contributor to cell membrane osmotic water permeability. Arteries are the physiological system where hydrostatic dominates osmotic pressure differences. In the present study, we show that the walls of large conduit arteries constitute the first example where hydrostatic pressure drives aquaporin-1-mediated transcellular/transendothelial flow. We studied cultured aortic endothelial cell monolayers and excised whole aortas of male Sprague-Dawley rats with intact and inhibited aquaporin-1 activity and with normal and knocked down aquaporin-1 expression. We subjected these systems to transmural hydrostatic pressure differences at zero osmotic pressure differences. Impaired aquaporin-1 endothelia consistently showed reduced engineering flow metrics (transendothelial water flux and hydraulic conductivity). In vitro experiments with tracers that only cross the endothelium paracellularly showed that changes in junctional transport cannot explain these reductions. Percent reductions in whole aortic wall hydraulic conductivity with either chemical blocking or knockdown of aquaporin-1 differed at low and high transmural pressures. This observation highlights how aquaporin-1 expression likely directly influences aortic wall mechanics by changing the critical transmural pressure at which its sparse subendothelial intima compresses. Such compression increases transwall flow resistance. Our endothelial and historic erythrocyte membrane aquaporin density estimates were consistent. In conclusion, aquaporin-1 significantly contributes to hydrostatic pressure-driven water transport across aortic endothelial monolayers, both in culture and in whole rat aortas. This transport, and parallel junctional flow, can dilute solutes that entered the wall paracellularly or through endothelial monolayer disruptions. Lower atherogenic precursor solute concentrations may slow their intimal entrainment kinetics.
Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure
Authors: Chen Jiqiu , Yaniz-Galende Elisa , Kagan Heather J. , Liang Lifan , Hekmaty Saboor , Giannarelli Chiara , Hajjar Roger
Published: February 2015

The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure.
Prediction of the impact of venoarterial extracorporeal membrane oxygenation on hemodynamics
Authors: Sakamoto Kazuo , Saku Keita , Kishi Takuya , Kakino Takamori , Tanaka Atsushi , Sakamoto Takafumi , Ide Tomomi , Sunagawa Kenji
Published: February 2015

Although venoarterial extracorporeal membrane oxygenation (ECMO) was developed to rescue patients with cardiogenic shock, the impact of ECMO on hemodynamics is often unpredictable and can lead to hemodynamic collapse. In this study, we developed a framework in which we incorporated ECMO into the extended Guyton's model of circulatory equilibrium and predicted hemodynamic changes in response to ECMO. We first determined the cardiac output (CO) curves of left and right heart (to generate the integrated CO curve) without ECMO in eight normal and seven dogs with left ventricular dysfunction. Using the CO curves obtained and standard parameters for the venous return surface, we predicted the circulatory equilibrium under various levels of ECMO support. The predicted total flow (native left heart flow plus ECMO flow), right atrial pressure (PRA), and left atrial pressure (PLA) matched well with those measured [total flow: coefficient of determination ( r2) = 0.99, standard error of estimate (SEE) = 5.8 ml·min−1·kg−1, PRA: r2 = 0.95, SEE = 0.23 mmHg, PLA: r2 = 0.99, SEE = 0.59 mmHg]. Lastly, we estimated the CO curves under ECMO support from minute changes in hemodynamics induced by change in ECMO. From the CO curves estimated, we predicted the circulatory equilibrium. The predicted total flow ( r2 = 0.93, SEE = 0.5 ml·min−1·kg−1), PRA ( r2 = 0.99, SEE = 0.54 mmHg), and PLA ( r2 = 0.95, SEE = 0.89 mmHg) matched reasonably well with those measured. A numerical simulation indicated that ECMO support may cause pulmonary edema, if right ventricular function is compromised. We conclude that the proposed framework may enhance the benefit and reduce the risk of ECMO support in patients with critical hemodynamic conditions.
Cerebrovascular effects of the thigh cuff maneuver
Authors: Panerai R. B. , Saeed N. P. , Robinson T. G.
Published: February 2015

Arterial hypotension can be induced by sudden release of inflated thigh cuffs (THC), but its effects on the cerebral circulation have not been fully described. In nine healthy subjects [aged 59 (9) yr], bilateral cerebral blood flow velocity (CBFV) was recorded in the middle cerebral artery (MCA), noninvasive arterial blood pressure (BP) in the finger, and end-tidal CO2 (ETCO2) with nasal capnography. Three THC maneuvers were performed in each subject with cuff inflation 20 mmHg above systolic BP for 3 min before release. Beat-to-beat values were extracted for mean CBFV, BP, ETCO2, critical closing pressure (CrCP), resistance-area product (RAP), and heart rate (HR). Time-varying estimates of the autoregulation index [ARI( t)] were also obtained using an autoregressive-moving average model. Coherent averages synchronized by the instant of cuff release showed significant drops in mean BP, CBFV, and RAP with rapid return of CBFV to baseline. HR, ETCO2, and ARI( t) were transiently increased, but CrCP remained relatively constant. Mean values of ARI( t) for the 30 s following cuff release were not significantly different from the classical ARI [right MCA 5.9 (1.1) vs. 5.1 (1.6); left MCA 5.5 (1.4) vs. 4.9 (1.7)]. HR was strongly correlated with the ARI( t) peak after THC release (in 17/22 and 21/24 recordings), and ETCO2 was correlated with the subsequent drop in ARI( t) (19/22 and 20/24 recordings). These results suggest a complex cerebral autoregulatory response to the THC maneuver, dominated by myogenic mechanisms and influenced by concurrent changes in ETCO2 and possible involvement of the autonomic nervous system and baroreflex.
Differences in angiotensin (1–7) between men and women
Authors: Sullivan Jennifer C. , Rodriguez-Miguelez Paula , Zimmerman Margaret A. , Harris Ryan A.
Published: February 2015

In experimental animal models of hypertension, angiotensin (1–7) [ANG-(1–7)] is higher in females compared with males; however, it is less clear whether the same applies to humans. Therefore, this study sought to compare circulating concentrations of ANG-(1–7) in apparently healthy men and women under normal physiological conditions. With the use of a cross-sectional experimental design, blood was collected in EDTA anticoagulant from 42 volunteers (21 men and 21 women; and age range, 19–48 yr) for analysis of plasma concentrations of ANG-(1–7) and ANG II. Blood pressure was measured and vascular endothelial function was determined ( n = 25) using the brachial artery flow-mediated dilation (FMD) test. As a result, women exhibited a higher circulating concentration of ANG-(1–7) ( P = 0.04) compared with men, whereas values of ANG II were similar between groups. Baseline arterial diameter, peak diameter, and shear rate were significantly greater ( P < 0.02) in men compared with women. No significant differences in FMD, FMD normalized for shear, or time to peak dilation were observed between men and women. In addition, a positive correlation between ANG-(1–7) and FMD ( P = 0.04) and negative association between ANG-(1–7) with ANG II ( P = 0.01) were only identified in men, whereas a positive relationship between ANG-(1–7) and diastolic blood pressure ( P = 0.03) was observed in women. In conclusion:, women exhibit significantly higher plasma concentrations of ANG-(1–7) compared with men. In addition, this study describes a relationship between ANG-(1–7), vascular function, and diastolic blood pressure that appears to be sex dependent.
Heme biosynthesis modulation via δ-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension
Authors: Alhawaj Raed , Patel Dhara , Kelly Melissa R. , Sun Dong , Wolin Michael S.
Published: February 2015

This study examines how heme biosynthesis modulation with δ-aminolevulinic acid (ALA) potentially functions to prevent 21-day hypoxia (10% oxygen)-induced pulmonary hypertension in mice and the effects of 24-h organoid culture with bovine pulmonary arteries (BPA) with the hypoxia and pulmonary hypertension mediator endothelin-1 (ET-1), with a focus on changes in superoxide and regulation of micro-RNA 204 (miR204) expression by src kinase phosphorylation of signal transducer and activator of transcription-3 (STAT3). The treatment of mice with ALA attenuated pulmonary hypertension (assessed through echo Doppler flow of the pulmonary valve, and direct measurements of right ventricular systolic pressure and right ventricular hypertrophy), increases in pulmonary arterial superoxide (detected by lucigenin), and decreases in lung miR204 and mitochondrial superoxide dismutase (SOD2) expression. ALA treatment of BPA attenuated ET-1-induced increases in mitochondrial superoxide (detected by MitoSox), STAT3 phosphorylation, and decreases in miR204 and SOD2 expression. Because ALA increases BPA protoporphyrin IX (a stimulator of guanylate cyclase) and cGMP-mediated protein kinase G (PKG) activity, the effects of the PKG activator 8-bromo-cGMP were examined and found to also attenuate the ET-1-induced increase in superoxide. ET-1 increased superoxide production and the detection of protoporphyrin IX fluorescence, suggesting oxidant conditions might impair heme biosynthesis by ferrochelatase. However, chronic hypoxia actually increased ferrochelatase activity in mouse pulmonary arteries. Thus, a reversal of factors increasing mitochondrial superoxide and oxidant effects that potentially influence remodeling signaling related to miR204 expression and perhaps iron availability needed for the biosynthesis of heme by the ferrochelatase reaction could be factors in the beneficial actions of ALA in pulmonary hypertension.
Pulmonary neuroepithelial bodies are polymodal airway sensors: Evidence for CO2/H+sensing
Authors: Livermore S. , Zhou Y. , Pan J. , Yeger H. , Nurse C. A. , Cutz E.
Published: February 2015

Pulmonary neuroepithelial bodies (NEB) in mammalian lungs are thought to function as airway O2sensors that release serotonin (5-HT) in response to hypoxia. Direct evidence that NEB cells also respond to airway hypercapnia/acidosis (CO2/H+) is presently lacking. We tested the effects of CO2/H+alone or in combination with hypoxia on 5-HT release from intact NEB cells in a neonatal hamster lung slice model. For the detection of 5-HT release we used carbon fiber amperometry. Fluorescence Ca2+imaging method was used to assess CO2/H+-evoked changes in intracellular Ca2+. Exposure to 10 and 20% CO2or pH 6.8–7.2 evoked significant release of 5-HT with a distinct rise in intracellular Ca2+in hamster NEBs. This secretory response was dependent on the voltage-gated entry of extracellular Ca2+. Moreover, the combined effects of hypercapnia and hypoxia were additive. Critically, an inhibitor of carbonic anhydrase (CA), acetazolamide, suppressed CO2/H+-mediated 5-HT release. The expression of mRNAs for various CA isotypes, including CAII, was identified in NEB cells from human lung, and protein expression was confirmed by immunohistochemistry using a specific anti-CAII antibody on sections of human and hamster lung. Taken together our findings provide strong evidence for CO2/H+sensing by NEB cells and support their role as polymodal airway sensors with as yet to be defined functions under normal and disease conditions.
PPAR-γ agonist rosiglitazone reverses perinatal nicotine exposure-induced asthma in rat offspring
Authors: Liu Jie , Sakurai Reiko , Rehan Virender K.
Published: February 2015

In a rat model, downregulation of homeostatic mesenchymal peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling following perinatal nicotine exposure contributes to offspring asthma, which can be effectively prevented by concomitant administration of PPAR-γ agonist rosiglitazone (RGZ). However, whether perinatal nicotine exposure-induced asthma can be reversed is not known. We hypothesized that perinatal nicotine exposure-induced asthma would be reversed by PPAR-γ agonist RGZ. Pregnant rat dams received either placebo or nicotine from embryonic day 6 until term. Following spontaneous delivery at term, dams were continued on the assigned treatments, up to postnatal day 21 (PND21). However, at delivery, pups were divided into two groups; one group received placebo, and the other group received RGZ from PND1 to PND21. At PND21, pulmonary function and the expression of mesenchymal markers of airway contractility (α-smooth muscle actin, calponin, fibronectin, collagen I, and collagen III) were determined by immunoblotting and immunostaining for the evidence of reversibility of perinatal nicotine exposure-induced lung effects. Compared with controls, perinatal nicotine exposure caused 1) a significant increase in airway resistance and a decrease in airway compliance following methacholine challenge, 2) a significant increase in acetylcholine-induced tracheal constriction, and 3) increased pulmonary and tracheal expression of the mesenchymal markers of contractility. Treatment with RGZ, starting on PND1, reversed all of the nicotine-induced molecular and functional pulmonary effects, virtually normalizing the pulmonary phenotype of the treated animals. We conclude that perinatal nicotine exposure-induced functional and molecular alterations in upper and lower airways can be reversed by PPAR-γ agonist RGZ, allowing an effective intervention even when started postnatally.
Sirt1 restrains lung inflammasome activation in a murine model of sepsis
Authors: Gao Rong , Ma Zhongsen , Hu Yuxin , Chen Jiao , Shetty Sreerama , Fu Jian
Published: February 2015

Excessive inflammation is a major cause of organ damage during sepsis. The elderly are highly susceptible to sepsis-induced organ injury. Sirt1 expression is reduced during aging. In the present study, we investigated the role of Sirt1, a histone deacetylase, in controlling inflammatory responses in a murine sepsis model induced by cecal ligation and puncture (CLP). We examined lung inflammatory signaling in inducible Sirt1 knockout (Sirt1−/−) mice and wild-type littermates (Sirt1+/+) after CLP. Our results demonstrated that Sirt1 deficiency led to severe lung inflammatory injury. To further investigate molecular mechanisms of Sirt1 regulation of lung inflammatory responses in sepsis, we conducted a series of experiments to assess lung inflammasome activation after CLP. We detected increased lung inflammatory signaling including NF-κB, signal transducer and activator of transcription 3, and ERK1/2 activation in Sirt1−/− mice after CLP. Furthermore, inflammasome activity was increased in Sirt1−/− mice after CLP, as demonstrated by increased IL-1β and caspase-7 cleavage and activation. Aggravated inflammasome activation in Sirt1−/− mice was associated with the increased production of lung proinflammatory mediators, including ICAM-1 and high-mobility group box 1, and further disruption of tight junctions and adherens junctions, as demonstrated by dramatic reduction of lung claudin-1 and vascular endothelial-cadherin expression, which was associated with the upregulation of matrix metallopeptidase 9 expression. In summary, our results suggest that Sirt1 suppresses acute lung inflammation during sepsis by controlling inflammasome activation pathway.
Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure
Authors: Goss Kara N. , Cucci Anthony R. , Fisher Amanda J. , Albrecht Marjorie , Frump Andrea , Tursunova Roziya , Gao Yong , Brown Mary Beth , Petrache Irina , Tepper Robert S. , Ahlfeld Shawn K. , Lahm Tim
Published: February 2015

The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults.
Influence of blood flow occlusion on muscle oxygenation characteristics and the parameters of the power-duration relationship
Authors: Broxterman R. M. , Ade C. J. , Craig J. C. , Wilcox S. L. , Schlup S. J. , Barstow T. J.
Published: February 2015

It was previously (Monod H, Scherrer J. Ergonomics 8: 329–338, 1965) postulated that blood flow occlusion during exercise would reduce critical power (CP) to 0 Watts (W), while not altering the curvature constant (W′). We empirically assessed the influence of blood flow occlusion on CP, W′, and muscle oxygenation characteristics. Ten healthy men (age: 24.8 ± 2.6 yr; height: 180 ± 5 cm; weight: 84.6 ± 10.1 kg) completed four constant-power handgrip exercise tests during both control blood flow (control) and blood flow occlusion (occlusion) for the determination of the power-duration relationship. Occlusion CP (−0.7 ± 0.4 W) was significantly ( P < 0.001) lower than control CP (4.1 ± 0.7 W) and significantly ( P < 0.001) lower than 0 W. Occlusion W′ (808 ± 155 J) was significantly ( P < 0.001) different from control W′ (558 ± 129 J), and all 10 subjects demonstrated an increased occlusion W′ with a mean increase of ∼49%. The present findings support the aerobic nature of CP. The findings also demonstrate that the amount of work that can be performed above CP is constant for a given condition, but can vary across conditions. Moreover, this amount of work that can be performed above CP does not appear to be the determinant of W′, but rather a consequence of the depletion of intramuscular energy stores and/or the accumulation of fatigue-inducing metabolites, which limit exercise tolerance and determine W′.