bluuebunny/crossref_metadata_2025 huggingface dataset:
Organometallic pyrene-containing porphyrins: Synthesis, characterization, and non-covalent interactions with C60 fullerenes
Authors: Li Yang , Rhoda Hannah M. , Wertish Anthony M. , Nemykin Victor N.
Published: September 2016

A reaction between 5,10,15,20-tetra(4-hydroxyphenyl)porphyrin and 1-bromopyrene resulted in the formation of 5,10,15,20-tetra[4-(4-(pyrenyl-1)butoxy)phenyl]porphyrin (1), while cross-condensation between 4-(4-(pyrenyl-1)butoxy)benzaldehyde, ferrocenecaboxaldehyde, and pyrrole resulted in the formation of 5-ferrocenyl-10,15,20-tri[4-(4-(pyrenyl-1)butoxy)phenyl]porphyrin (2), 5,10-diferrocenyl-15,20-di[4-(4-(pyrenyl-1)butoxy)phenyl]porphyrin (3), and 5,15-diferrocenyl-10,20-di[4-(4-(pyrenyl-1)butoxy)phenyl]porphyrin (4). All pyrene-containing porphyrins were characterized by 1H NMR, UV-vis, MCD, and high-resolution ESI methods, while their electronic structures and the nature of the excited states were elucidated using density functional theory (DFT) and time-dependent DFT (TDDFT) calculations. The molecular structure of 1 and its fluorescence quenching upon the addition of C[Formula: see text] fullerene was also investigated using X-ray crystallography and steady-state fluorescence approaches.
Vertical intensity modulation for improved radiographic penetration and reduced exclusion zone
Authors: Bendahan J. , Langeveld W.G.J. , Bharadwaj V. , Amann J. , Limborg C. , Nosochkov Y.
Published: September 2016

In the present work, a method to direct the X-ray beam in real time to the desired locations in the cargo to increase penetration and reduce exclusion zone is presented. Cargo scanners employ high energy X-rays to produce radiographic images of the cargo. Most new scanners employ dual-energy to produce, in addition to attenuation maps, atomic number information in order to facilitate the detection of contraband. The electron beam producing the bremsstrahlung X-ray beam is usually directed approximately to the center of the container, concentrating the highest X-ray intensity to that area. Other parts of the container are exposed to lower radiation levels due to the large drop-off of the bremsstrahlung radiation intensity as a function of angle, especially for high energies (>6 MV). This results in lower penetration in these areas, requiring higher power sources that increase the dose and exclusion zone. The capability to modulate the X-ray source intensity on a pulse-by-pulse basis to deliver only as much radiation as required to the cargo has been reported previously. This method is, however, controlled by the most attenuating part of the inspected slice, resulting in excessive radiation to other areas of the cargo. A method to direct a dual-energy beam has been developed to provide a more precisely controlled level of required radiation to highly attenuating areas. The present method is based on steering the dual-energy electron beam using magnetic components on a pulse-to-pulse basis to a fixed location on the X-ray production target, but incident at different angles so as to direct the maximum intensity of the produced bremsstrahlung to the desired locations. The details of the technique and subsystem and simulation results are presented.
Detectors for in vivo range and dose verification in proton therapy
Authors: Alarcon R. , Blyth D. , Galyaev E. , Holmes J. , Ice L. , Randall G. , Bues M. , Fatyga M.
Published: September 2016

Particle detection instrumentation to address the in vivo verifications of proton dose and range is under development as part of a proton therapy research program focused on patient quality assurance. For in vivo proton range verification, a collimated gamma detector array is under construction to indirectly measure the position of the Bragg peak for each proton beam spot to within 1–2 mm precision. For dose flux verification, a proton fluence detector based on the technology of the Micromegas is under construction. This detector has an active area of about 100 cm2, coordinate resolution of better than 1 mm, and handling of incident proton beam fluxes of 109–1013 particles/s.
Rotators for matching non-symmetric ion-therapy beams to rotating gantries
Authors: Pavlovič Márius , Bokor Jozef , Šagátová Andrea
Published: September 2016

The paper deals with special ion-optical matching sections called “rotators” for matching non-symmetric beams to rotating ion-therapy gantries. General matrix analysis of the problem is formulated resulting in a specific set of ion-optical constraints that must be fulfilled by the rotator transfer matrix. Possible ways of fitting these ion-optical constraints are discussed and illustrated by several examples of suitable rotator lattices. Each lattice is representing a different type of rotator, e.g. point-to-point imaging lattice or parallel-to-point imaging lattice. Optimization of the rotator lattice with respect to its total length is discussed, and the most compact solutions are presented as well.
Detection of fast neutrons from D–T nuclear reaction using a 4H–SiC radiation detector
Authors: Zatko Bohumir , Sagatova Andrea , Sedlackova Katarina , Necas Vladimir , Dubecky Frantisek , Solar Michael , Granja Carlos
Published: September 2016

The particle detector based on a high purity epitaxial layer of 4H–SiC exhibits promising properties in detection of various types of ionizing radiation. Due to the wide band gap of 4H–SiC semiconductor material, the detector can reliably operate at room and also elevated temperatures. In this work we focused on detection of fast neutrons generated the by D–T (deuterium–tritium) nuclear reaction. The epitaxial layer with a thickness of 105 [Formula: see text]m was used as a detection part. A circular Schottky contact of a Au/Ni double layer was evaporated on both sides of the detector material. The detector structure was characterized by current-voltage and capacitance-voltage measurements, at first. The results show very low current density (<0.1 nA/cm[Formula: see text] at room temperature and good homogeneity of free carrier concentration in the investigated depth. The fabricated detectors were tested for detection of fast neutrons generated by the D–T reaction. The energies of detected fast neutrons varied from 16.0 MeV to 18.3 MeV according to the acceleration potential of deuterons, which increased from 600 kV up to 2 MV. Detection of fast neutrons in the SiC detector is caused by the elastic and inelastic scattering on the silicon or carbide component of the detector material. Another possibility that increases the detection efficiency is the use of a conversion layer. In our measurements, we glued a HDPE (high density polyethylene) conversion layer on the detector Schottky contact to transform fast neutrons to protons. Hydrogen atoms contained in the conversion layer have a high probability of interaction with neutrons through elastic scattering. Secondary generated protons flying to the detector can be easily detected. The detection properties of detectors with and without the HDPE conversion layer were compared.
Two neutron correlations in photo-fission
Authors: Dale D. S. , Kosinov O. , Forest T. , Burggraf J. , Stave S. , Warren G. , Starovoitova V.
Published: September 2016

A large body of experimental work has established the strong kinematical correlation between fission fragments and fission neutrons. Here, we report on the progress of investigations of the potential for strong two neutron correlations arising from the nearly back-to-back nature of the two fission fragments that emit these neutrons in the photo-fission process. In initial measurements, a pulsed electron linear accelerator was used to generate bremsstrahlung photons that impinged upon an actinide target, and the energy and opening angle distributions of coincident neutrons were measured using a large acceptance neutron detector array. A planned comprehensive set of measurements of two neutron correlations in the photo-fission of actinides is expected to shed light on several fundamental aspects of the fission process including the multiplicity distributions associated with the light and heavy fission fragments, the nuclear temperatures of the fission fragments, and the mass distribution of the fission fragments as a function of energy released. In addition to these measurements providing important nuclear data, the unique kinematics of fission and the resulting two neutron correlations have the potential to be the basis for a new tool to detect fissionable materials. A key technical challenge of this program arises from the need to perform coincidence measurements with a low duty factor, pulsed electron accelerator. This has motivated the construction of a large acceptance neutron detector array, and the development of data analysis techniques to directly measure uncorrelated two neutron backgrounds.
Geodynamical framework and hydrocarbon plays of a salt giant: the NW Mediterranean Basin
Authors: Granado Pablo , Urgeles Roger , Sàbat Francesc , Albert-Villanueva Eduard , Roca Eduard , Muñoz Josep Anton , Mazzuca Nicoletta , Gambini Roberto
Published: September 2016

The NW Mediterranean Basin developed during the Oligocene–Miocene rifting of the Eastern Iberian–European magma-poor continental margin. The margin developed as a result of back-arc extension associated with the rollback of the retreating Calabrian–Tethys subduction zone. Reinterpretation of 2D regional seismic reflection data suggests that rifting took place by hyperextension of the Iberian–European lithosphere. This process led to the seawards arrangement of distinct crustal domains: namely, proximal, necking and distal. The late post-rift Messinian salinity crisis (MSC) gave rise to significant margin erosion and canyon incision, the lowstand sedimentary by-products of which were largely deposited prior to the Messinian evaporitic sequences. Mesozoic–Cenozoic and Messinian–Recent salt tectonics events have been recognized. A regional hydrocarbon play concept is proposed here for shelf–deep-water settings, including pre-salt, Messinian and post-salt plays.
The Messinian record of Spanish onshore and offshore data (Atlantic Ocean and Western Mediterranean Sea)
Authors: Martínez del Olmo W. , Martín D.
Published: September 2016

Spanish territory offers a remarkable location to study the Messinian salinity crisis (MSC). So much so, that sub-basins and open margins to the Mediterranean Sea and the Atlantic Ocean can be studied from outcrop data, 2D and 3D seismic surveys, and well logs. From the analysed data, it can be determined that the Messinian sediments are involved in three third-order depositional sequences: (1) Late Tortonian–Messinian, with temperate carbonates, coral reefs and sandy turbidities; (2) Messinian, with on- and offshore deposition of shallow-marine evaporate and isotopic freshwater facies; and (3) Messinian–Early Pliocene, comprising deposits of sandy (Atlantic) and gypsum-sandy turbidites (Mediterranean) that filled incised valleys. From seismic images, the best exploration opportunities involve the lowstand systems tracts (LST), the carbonates and different facies under deep-water evaporates. For these, however, the problem is to establish the source rock, by: (a) the presence of Messinian deep-water paper shales; (b) the gas having to be biogenic in the absence of paper shales; and (c) reaching the maturity level in areas with limestone and coral reef prospects. The above possibilities come from our conception of the Messinian crisis, which was caused by two different episodes: climatic change in a restricted, but not desiccated, Mediterranean Sea, following by multiple sea-level falls and the deposition of their correlative LST turbiditic systems.
Fault reactivation in travertine and its impact on hydraulic transmissibility: laboratory experiments and mesoscale structures
Authors: Giwelli A. , Esteban L. , Delle Piane C. , Clennell M. B.
Published: September 2016

Direct shear experiments were undertaken to investigate the effect of faulting and reactivation on the hydromechanical characteristics of faults in continental carbonate samples. The tested rock is a travertine of continental, microbial origin with a calcite content of 99 wt%, with a strongly laminated texture. Analyses of the intact and sheared samples performed using medical X-ray computed tomography (CT) revealed that the porosity is mainly composed of subplanar pores and vugs. Permeability is high along the laminations, controlled by interconnected pores and fractures. The travertine is a lithological analogue for Aptian pre-salt oil reservoir rocks found in South Atlantic offshore basins. Three samples, with dimensions of 240 × 110 × 150 mm, were sheared to a maximum displacement of 120 mm under different levels of effective vertical stress (6–45 MPa), resulting in the formation of cataclastic fault gouge surrounded by a dense fracture network. A new experimental method was used to reactivate the artificially formed fault by performing cyclic vertical loading at different shear displacements on a previously sheared sample, while keeping a constant pore-pressure differential throughout the test.

Pore-fluid responses across the fault zone were monitored continuously during both deformation (dynamic transmissibility) and hold periods (static transmissibility). Results show that the transmissibility reduces in all the samples for all values of the applied effective vertical stress and during shear reversal. The static transmissibility also decreases over time, which may be a result of creep deformation or the blocking of pore channels with gouge material. Our results indicate that once the gouge material is developed in the core of a carbonate fault zone, the dynamic transmissibility across that fault is permanently decreased, with little dependence on subsequent kinematics of reactivation, or changes in stress, so long as the gouge zone is not breached by a new structure.
Alteration and submergence of basalts in Kachchh, Gujarat, India: implications for the role of the Deccan Traps in the India–Seychelles break-up
Authors: Mitra Souvik , Mitra Kaushik , Gupta Saibal , Bhattacharya Satadru , Chauhan Prakash , Jain Nirmala
Published: September 2016

The Deccan Trap flood basalt volcanism has commonly been considered to have initiated the break-up of India from the Seychelles (
c.
62.5 Ma). In Kachchh, Gujarat, western India, the sedimentary succession in the Paleocene Matanomadh Formation was deposited on highly weathered Deccan Trap basalts that were altered to kaolinite before basin formation. This contrasts with the weathering pattern on flat-topped hills of the Deccan Traps outside the Cenozoic rift basins in the Kachchh region and other parts of India, where basalt is dominantly altered to smectitic minerals. As basalts that are altered to smectite and kaolinite occur just across the faults that bound the Matanomadh Basin, the differential weathering cannot be attributed to climate. Geochemical modelling shows that kaolinite stabilizes in preference to smectite if CO
2
- and O
2
-buffered rainwater interacts with well-drained basaltic rock at high water:rock ratios. Such conditions can be accomplished by rainfall on a slope created by Cenozoic rifting that exposes the graben flank and basin floor basalts to continuously flowing water, the composition of which is buffered by equilibration with the atmosphere. As the rift post-dates both the eruption of the basalts and subsequent smectite formation, the associated extensional tectonics must be unrelated to flood basalt volcanism, and is most likely to correspond to the India–Seychelles break-up.
A Scalable Algebraic Method to Infer Quadratic Invariants of Switched Systems
Authors: Allamigeon Xavier , Gaubert Stéphane , Stott Nikolas , Goubault Éric , Putot Sylvie
Published: September 2016

We present a new numerical abstract domain based on ellipsoids designed for the formal verification of switched linear systems. Unlike the existing approaches, this domain does not rely on a user-given template. We overcome the difficulty that ellipsoids do not have a lattice structure by exhibiting a canonical operator overapproximating the union. This operator is the only one that permits the performance of analyses that are invariant with respect to a linear transformation of state variables. It provides the minimum volume ellipsoid enclosing two given ellipsoids. We show that it can be computed in
O
(
n
3
) elementary algebraic operations. We finally develop a fast nonlinear power-type algorithm, which allows one to determine sound quadratic invariants on switched systems in a tractable way, by solving fixed-point problems over the space of ellipsoids. We test our approach on several benchmarks, and compare it with the standard techniques based on linear matrix inequalities, showing an important speedup on typical instances.
Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants
Authors: Kao Liyo , Azimov Rustam , Shao Xuesi M. , Frausto Ricardo F. , Abuladze Natalia , Newman Debra , Aldave Anthony J. , Kurtz Ira
Published: September 2016

Congenital hereditary endothelial dystrophy (CHED), Harboyan syndrome (CHED with progressive sensorineural deafness), and potentially a subset of individuals with late-onset Fuchs' endothelial corneal dystrophy are caused by mutations in the SLC4A11 gene that results in corneal endothelial cell abnormalities. Originally classified as a borate transporter, the function of SLC4A11 as a transport protein remains poorly understood. Elucidating the transport function(s) of SLC4A11 is needed to better understand how its loss results in the aforementioned posterior corneal dystrophic disease processes. Quantitative PCR experiments demonstrated that, of the three known human NH2-terminal variants, SLC4A11-C is the major transcript expressed in human corneal endothelium. We studied the expression pattern of the three variants in mammalian HEK-293 cells and demonstrated that the SLC4A11-B and SLC4A11-C variants are plasma membrane proteins, whereas SLC4A11-A is localized intracellularly. SLC4A11-B and SLC4A11-C were shown to be multifunctional ion transporters capable of transporting H+ equivalents in both a Na+-independent and Na+-coupled mode. In both transport modes, SLC4A11-C H+ flux was significantly greater than SLC4A11-B. In the presence of ammonia, SLC4A11-B and SLC4A11-C generated inward currents that were comparable in magnitude. Chimera SLC4A11-C-NH2-terminus-SLC4A11-B experiments demonstrated that the SLC4A11-C NH2-terminus functions as an autoactivating domain, enhancing Na+-independent and Na+-coupled H+ flux without significantly affecting the electrogenic NH3-H( n)+ cotransport mode. All three modes of transport were significantly impaired in the presence of the CHED causing p.R109H (SLC4A11-C numbering) mutation. These complex ion transport properties need to be addressed in the context of corneal endothelial disease processes caused by mutations in SLC4A11.
Adaptation to a high-protein diet progressively increases the postprandial accumulation of carbon skeletons from dietary amino acids in rats
Authors: Stepien Magdalena , Azzout-Marniche Dalila , Even Patrick C. , Khodorova Nadezda , Fromentin Gilles , Tomé Daniel , Gaudichon Claire
Published: September 2016

We aimed to determine whether oxidative pathways adapt to the overproduction of carbon skeletons resulting from the progressive activation of amino acid (AA) deamination and ureagenesis under a high-protein (HP) diet. Ninety-four male Wistar rats, of which 54 were implanted with a permanent jugular catheter, were fed a normal protein diet for 1 wk and were then switched to an HP diet for 1, 3, 6, or 14 days. On the experimental day, they were given their meal containing a mixture of 20 U-[15N]-[13C] AA, whose metabolic fate was followed for 4 h. Gastric emptying tended to be slower during the first 3 days of adaptation. 15N excretion in urine increased progressively during the first 6 days, reaching 29% of ingested protein. 13CO2 excretion was maximal, as early as the first day, and represented only 16% of the ingested proteins. Consequently, the amount of carbon skeletons remaining in the metabolic pools 4 h after the meal ingestion progressively increased to 42% of the deaminated dietary AA after 6 days of HP diet. In contrast, 13C enrichment of plasma glucose tended to increase from 1 to 14 days of the HP diet. We conclude that there is no oxidative adaptation in the early postprandial period to an excess of carbon skeletons resulting from AA deamination in HP diets. This leads to an increase in the postprandial accumulation of carbon skeletons throughout the adaptation to an HP diet, which can contribute to the sustainable satiating effect of this diet.
Intramyocellular ceramides and skeletal muscle mitochondrial respiration are partially regulated by Toll-like receptor 4 during hindlimb unloading
Authors: Kwon Oh Sung , Nelson Daniel S. , Barrows Katherine M. , O'Connell Ryan M. , Drummond Micah J.
Published: September 2016

Physical inactivity and disuse result in skeletal muscle metabolic disruption, including insulin resistance and mitochondrial dysfunction. The role of the Toll-like receptor 4 (TLR4) signaling pathway in contributing to metabolic decline with muscle disuse is unknown. Therefore, our goal was to determine whether TLR4 is an underlying mechanism of insulin resistance, mitochondrial dysfunction, and skeletal muscle ceramide accumulation following muscle disuse in mice. To address this hypothesis, we subjected ( n = 6–8/group) male WT and TLR4−/−mice to 2 wk of hindlimb unloading (HU), while a second group of mice served as ambulatory wild-type controls (WT CON, TLR4−/−CON). Mice were assessed for insulin resistance [homeostatic model assessment-insulin resistance (HOMA-IR), glucose tolerance], and hindlimb muscles (soleus and gastrocnemius) were used to assess muscle sphingolipid abundance, mitochondrial respiration [respiratory control ratio (RCR)], and NF-κB signaling. The primary finding was that HU resulted in insulin resistance, increased total ceramides, specifically Cer18:0 and Cer20:0, and decreased skeletal muscle mitochondrial respiration. Importantly, TLR4−/−HU mice were protected from insulin resistance and altered NF-κB signaling and were partly resistant to muscle atrophy, ceramide accumulation, and decreased RCR. Skeletal muscle ceramides and RCR were correlated with insulin resistance. We conclude that TLR4 is an upstream regulator of insulin sensitivity, while partly upregulating muscle ceramides and worsening mitochondrial respiration during 2 wk of HU.
Temporal deletion ofAqp11in mice is linked to the severity of cyst-like disease
Authors: Rützler Michael , Rojek Aleksandra , Damgaard Mads Vammen , Andreasen Arne , Fenton Robert A. , Nielsen Søren
Published: September 2016

Aquaporin 11 (AQP11) is a channel protein with unknown biological function that is expressed in multiple tissues, including the kidney proximal tubule (PT) epithelium. Constitutive deletion of Aqp11 in mice ( Aqp11−/−) results in early postnatal vacuolization in the PT and development of apparent cysts at 2 wk of age. Electron microscopy of adult Aqp11−/−mouse PT cells revealed a dilated rough endoplasmic reticulum. These changes may cause renal failure and premature death. This study examined 1) whether postnatal deletion of Aqp11 affects PT injury and cyst formation, 2) the temporal role of Aqp11 deletion on cyst development, and 3) the nature of apparent cysts. Tamoxifen-inducible Aqp11−/−mice were generated (Ti- Aqp11−/−). Deletion of Aqp11 at postnatal days (P) P2, P4, P6, P8, and P12 was investigated. Deranged renal development, especially in kidney cortex, PT cell vacuolization, and apparent tubular cysts developed only in mice where Aqp11 gene disruption was induced until P8. Aqp11 gene deletion from P12 onward did not result in a clear deficiency in renal development, PT injury, or cyst formation. Intraperitoneal injection of biotinylated-dextran (10 kDa) into adult mice resulted in extensive endocytic dextran uptake in both cystic Aqp11−/−and control PT epithelium, respectively. This suggests that apparent cysts are not membrane-enclosed structures but represent PT dilations. We conclude that Aqp11−/−mice develop cyst-like dilated proximal tubules without documented cysts at time of death.
Loss of endothelin B receptor function impairs sodium excretion in a time- and sex-dependent manner
Authors: Johnston Jermaine G. , Speed Joshua S. , Jin Chunhua , Pollock David M.
Published: September 2016

Recent studies suggested a direct link between circadian rhythms and regulation of sodium excretion. Endothelin-1 (ET-1) regulates sodium balance by promoting natriuresis through the endothelin B receptor (ETB) in response to increased salt in the diet, but the effect that the time of day has on this natriuretic response is not known. Therefore, this study was designed to test the hypothesis that ETBreceptor activation contributes to the diurnal control of sodium excretion and that sex differences contribute to this control as well. Twelve-hour urine collections were used to measure sodium excretion. On day 3 of the experiment, a NaCl load (900 μeq) was given by oral gavage either at Zeitgeber time [ZT] 0 (inactive period) or ZT12 (active period) to examine the natriuretic response to the acute salt load. Male and female ETB-deficient (ETBdef) rats showed an impaired natriuretic response to a salt load at ZT0 compared with their respective transgenic controls (Tg cont). Male ETBdef rats showed a delayed natriuretic response to a salt load given at ZT12 compared with male Tg cont, a contrast to the prompt response shown by female ETBdef rats. Treatment with ABT-627, an ETAreceptor antagonist, improved the natriuretic response seen within the first 12 h of a ZT0 salt load in both sexes. These findings demonstrate that diurnal excretion of an acute salt load 1) requires ET-1 and the ETBreceptor, 2) is more evident in male vs. female rats, and 3) is opposed by the ETAreceptor.
Both CLIC4 and CLIC5A activate ERM proteins in glomerular endothelium
Authors: Tavasoli Mahtab , Al-Momany Abass , Wang Xin , Li Laiji , Edwards John C. , Ballermann Barbara J.
Published: September 2016

The chloride intracellular channel (CLIC) 5A is expressed at very high levels in renal glomeruli, in both endothelial cells (EC) and podocytes. CLIC5A stimulates Rac1- and phosphatidylinositol (4,5)-bisphosphate-dependent ERM (ezrin, radixin, moesin) activation. ERM proteins, in turn, function in lumen formation and in the development of actin-based cellular projections. In mice lacking CLIC5A, ERM phosphorylation is profoundly reduced in podocytes, but preserved in glomerular EC. Since glomerular EC also express CLIC4, we reasoned that, if CLIC4 activates ERM proteins like CLIC5A, then CLIC4 could compensate for the CLIC5A loss in glomerular EC. In glomeruli of CLIC5-deficient mice, CLIC4 expression was upregulated and colocalized with moesin and ezrin in glomerular EC, but not in podocytes. In cultured glomerular EC, CLIC4 silencing reduced ERM phosphorylation and cytoskeletal association, and expression of exogenous CLIC4 or CLIC5A rescued ERM de-phosphorylation due to CLIC4 silencing. In mice lacking either CLIC4 or CLIC5, ERM phosphorylation was retained in glomerular EC, but, in mice lacking both CLIC4 and CLIC5, glomerular EC ERM phosphorylation was profoundly reduced. Although glomerular EC fenestrae developed normally in dual CLIC4/CLIC5-deficient mice, the density of fenestrae declined substantially by 8 mo of age, along with the deposition of subendothelial electron-lucent material. The dual CLIC4/CLIC5-deficient mice developed spontaneous proteinuria, glomerular cell proliferation, and matrix deposition. Thus CLIC4 stimulates ERM activation and can compensate for CLIC5A in glomerular EC. The findings indicate that CLIC4/CLIC5A-mediated ERM activation is required for maintenance of the glomerular capillary architecture.
Nrf2-AKT interactions regulate heme oxygenase 1 expression in kidney epithelia during hypoxia and hypoxia-reoxygenation
Authors: Potteti Haranatha R. , Tamatam Chandramohan R. , Marreddy Rakesh , Reddy Narsa M. , Noel Sanjeev , Rabb Hamid , Reddy Sekhar P.
Published: September 2016

Ischemia-reperfusion (IR)-induced kidney injury is a major clinical problem, but its underlying mechanisms remain unclear. The transcription factor known as nuclear factor, erythroid 2-like 2 (NFE2L2 or Nrf2) is crucial for protection against oxidative stress generated by pro-oxidant insults. We have previously shown that Nrf2 deficiency enhances susceptibility to IR-induced kidney injury in mice and that its upregulation is protective. Here, we examined Nrf2 target antioxidant gene expression and the mechanisms of its activation in both human and murine kidney epithelia following acute (2 h) and chronic (12 h) hypoxia and reoxygenation conditions. We found that acute hypoxia modestly stimulates and chronic hypoxia strongly stimulates Nrf2 putative target HMOX1 expression, but not that of other antioxidant genes. Inhibition of AKT1/2 or ERK1/2 signaling blocked this induction; AKT1/2 but not ERK1/2 inhibition affected Nrf2 levels in basal and acute hypoxia-reoxygenation states. Unexpectedly, chromatin immunoprecipitation assays revealed reduced levels of Nrf2 binding at the distal AB1 and SX2 enhancers and proximal promoter of HMOX1 in acute hypoxia, accompanied by diminished levels of nuclear Nrf2. In contrast, Nrf2 binding at the AB1 and SX2 enhancers significantly but differentially increased during chronic hypoxia and reoxygenation, with reaccumulation of nuclear Nrf2 levels. Small interfering-RNA-mediated Nrf2 depletion attenuated acute and chronic hypoxia-inducible HMOX1 expression, and primary Nrf2-null kidney epithelia showed reduced levels of HMOX1 induction in response to both acute and chronic hypoxia. Collectively, our data demonstrate that Nrf2 upregulates HMOX1 expression in kidney epithelia through a distinct mechanism during acute and chronic hypoxia reoxygenation, and that both AKT1/2 and ERK1/2 signaling are required for this process.
Human epithelial Na+channel missense variants identified in the GenSalt study alter channel activity
Authors: Ray Evan C. , Chen Jingxin , Kelly Tanika N. , He Jiang , Hamm L. Lee , Gu Dongfeng , Shimmin Lawrence C. , Hixson James E. , Rao Dabeeru C. , Sheng Shaohu , Kleyman Thomas R.
Published: September 2016

Mutations in genes encoding subunits of the epithelial Na+channel (ENaC) can cause early onset familial hypertension, demonstrating the importance of this channel in modulating blood pressure. It remains unclear whether other genetic variants resulting in subtler alterations of channel function result in hypertension or altered sensitivity of blood pressure to dietary salt. This study sought to identify functional human ENaC variants to examine how these variants alter channel activity and to explore whether these variants are associated with altered sensitivity of blood pressure to dietary salt. Six-hundred participants of the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study with salt-sensitive or salt-resistant blood pressure underwent sequencing of the genes encoding ENaC subunits. Functional effects of identified variants were examined in a Xenopus oocyte expression system. Variants that increased channel activity included three in the gene encoding the α-subunit (αS115N, αR476W, and αV481M), one in the β-subunit (βS635N), and one in the γ-subunit (γL438Q). One α-subunit variant (αA334T) and one γ-subunit variant (βD31N) decreased channel activity. Several α-subunit extracellular domain variants altered channel inhibition by extracellular Na+(Na+self-inhibition). One variant (αA334T) decreased and one (αV481M) increased cell surface expression. Association between these variants and salt sensitivity did not reach statistical significance. This study identifies novel functional human ENaC variants and demonstrates that some variants alter channel cell surface expression and/or Na+self-inhibition.
Extracellular vesicles in diagnosis and therapy of kidney diseases
Authors: Zhang Wei , Zhou Xiangjun , Zhang Hao , Yao Qisheng , Liu Yutao , Dong Zheng
Published: September 2016

Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.
Implications of cellular models of dopamine neurons for disease
Authors: Canavier Carmen C. , Evans Rebekah C. , Oster Andrew M. , Pissadaki Eleftheria K. , Drion Guillaume , Kuznetsov Alexey S. , Gutkin Boris S.
Published: September 2016

This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models.
Experience-dependent plasticity of excitatory and inhibitory intertectal inputs in Xenopus tadpoles
Authors: Gambrill Abigail C. , Faulkner Regina L. , Cline Hollis T.
Published: September 2016

Communication between optic tecta/superior colliculi is thought to be required for sensorimotor behaviors by comparing inputs across the midline; however, the development of and the role of visual experience in the function and plasticity of intertectal connections are unclear. We combined neuronal labeling, in vivo time-lapse imaging, and electrophysiology to characterize the structural and functional development of intertectal axons and synapses in Xenopus tadpole optic tectum. We find that intertectal connections are established early during optic tectal circuit development. We determined the neurotransmitter identity of intertectal neurons using both rabies virus-mediated tracing combined with post hoc immunohistochemistry and electrophysiology. Excitatory and inhibitory intertectal neuronal somata are similarly distributed throughout the tectum. Excitatory and inhibitory intertectal axons are structurally similar and elaborate broadly in the contralateral tectum. We demonstrate that intertectal and retinotectal axons converge onto tectal neurons by recording postsynaptic currents after stimulating intertectal and retinotectal inputs. Cutting the intertectal commissure removes synaptic responses to contralateral tectal stimulation. In vivo time-lapse imaging demonstrated that visual experience drives plasticity in intertectal bouton size and dynamics. Finally, visual experience drives the maturation of excitatory intertectal inputs by increasing AMPA-to- N-methyl-d-aspartate (NMDA) ratios, comparable to experience-dependent maturation of retinotectal inputs, and coordinately increases intertectal GABA receptor-mediated currents. These data indicate that visual experience regulates plasticity of excitatory and inhibitory intertectal inputs, maintaining the balance of excitatory to inhibitory intertectal input. These studies place intertectal inputs as key players in tectal circuit development and suggest that they may play a role in sensory information processing critical to sensorimotor behaviors.
Photocatalytic Activity and Optical Properties of Blue Persistent Phosphors under UV and Solar Irradiation
Authors: García C. R. , Diaz-Torres L. A. , Oliva J. , Romero M. T. , Salas P.
Published: September 2016

Blue phosphorescent strontium aluminosilicate powders were prepared by combustion synthesis route and a postannealing treatments at different temperatures. X-ray diffraction analysis showed that phosphors are composed of two main hexagonal phases: SrAl2O4and Sr3Al32O51. The morphology of the phosphors changed from micrograins (1000°C) to a mixture of bars and hexagons (1200°C) and finally to only hexagons (1300°C) as the annealing temperature is increased. Photoluminescence spectra showed a strong blue-green phosphorescent emission centered atλem=455 nm, which is associated with4f65d1→4f6  (8S7/2)transition of the Eu2+. The sample annealed at 1200°C presents the highest luminance value (40 Cd/m2) with CIE coordinates (0.1589, 0.1972). Also, the photocatalytic degradation of methylene blue (MB) under UV light (at 365 nm) was monitored. Samples annealed at 1000°C and 1300°C presented the highest percentage of degradation (32% and 38.5%, resp.) after 360 min. In the case of photocatalytic activity under solar irradiation, the samples annealed at 1000°C, 1150°C, and 1200°C produced total degradation of MB after only 300 min. Hence, the results obtained with solar photocatalysis suggest that our powders could be useful for water cleaning in water treatment plants.
Molecular Characterization of LRB7 Gene and a Water Channel Protein TIP2 inChorispora bungeana
Authors: Li Ming , Liang Zhaoxu , Di Cuixia , Fang Weikuan , Wu Kaichao , Chen Maoshan , He Shanshan , Zeng Yuan , Jing Yan , Liang Jun , Tan Fang , Li Song , Chen Tuo , Liu Guangxiu , An Lizhe
Published: September 2016

Background. Water channel proteins, also called aquaporins, are integral membrane proteins from major intrinsic protein (MIP) family and involved in several pathways including not only water transport but also cell signaling, reproduction, and photosynthesis. The full cDNA and protein sequences of aquaporin inChorispora bungeanaFisch. & C.A. Mey (C. bungeana) are still unknown.Results. In this study, PCR and rapid amplification of cDNA ends approaches were used to clone the full cDNA of LRB7 (GenBank accession number: EU636988) ofC. bungeana. Sequence analysis indicated that it was 1235 bp, which had two introns and encoded a protein of 250 amino acids. Structure analysis revealed that the protein had two conserved NPA motifs, one of which is MIP signature sequence (SGxHxNPAVT), six membrane helix regions, and additional membrane-embedded domains. Phylogenetic analysis suggested that the protein was from TIP2 subgroup. Surprisingly, semiquantitative RT-PCR experiment and western blot analysis showed that LRB7 and TIP2 were only detectable in roots, unlikeArabidopsisandRaphanus. Connecting with our previous studies, LRB7 was supported to associate with chilling-tolerance inC. bungeana.Conclusion. This is the first time to characterize the full sequences of LRB7 gene and water channel protein inC. bungeana. Our findings contribute to understanding the water transports in plants under low temperatures.
Doxycycline and Benznidazole Reduce the Profile of Th1, Th2, and Th17 Chemokines and Chemokine Receptors in Cardiac Tissue from ChronicTrypanosoma cruzi-Infected Dogs
Authors: Paula Costa Guilherme de , Lopes Laís Roquete , Silva Maria Cláudia da , Horta Aline Luciano , Pontes Washington Martins , Milanezi Cristiane M. , Guedes Paulo Marcos da Mata , Lima Wanderson Geraldo de , Schulz Richard , Silva João Santana da , Talvani Andre
Published: September 2016

Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by theTrypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain ofT. cruziand grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle. After 14 months of infection, hearts were excised and processed for qPCR analysis of Th1 (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL11), Th2 (CCL1, CCL17, CCL24, and CCL26), Th17 (CCL20) CKs, Th1 (CCR5, CCR6, and CXCR3), and Th2/Th17 (CCR3, CCR4, and CCR8) CKR, as well as IL-17.T. cruziinfection increases CCL1, CCL2, CCL4, CCL5, CCL17, CXCL10, and CCR5 expression in the heart. Dox, Bz, or Dox + Bz treatments cause a reversal of CK and CKR and reduce the expression of CCL20, IL-17, CCR6, and CXCR3. Our data reveal an immune modulatory effect of Dox with Bz, during the chronic phase of infection suggesting a promising therapy for cardiac protection.
Delirious Mania Associated with Autoimmune Gastrothyroidal Syndrome of a Mid-Life Female: The Role of Hashimoto Encephalopathy and a 3-Year Follow-Up including Serum Autoantibody Levels
Authors: Bonnet Udo , Selle Claudia , Kuhlmann Ralf
Published: September 2016

We report the case study of a 57-year-old Caucasian female with steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), commonly termed Hashimoto encephalopathy (HE). This presentation includes one of the longest lasting follow-up studies of HE considering the neuropsychiatric symptoms (here delirium, mania, and EEG-slowing) and their relation to serum autoantibody levels. Antithyroid-peroxidase autoantibodies, the hallmark of autoimmune thyroiditis, were found in the serum and also in the cerebrospinal fluid. Diagnostic analyses found no evidence of limbic encephalopathies characterized by serum antibodies against intracellular, synaptic, or further cell surface antigenic targets, neoplasm, and connective tissue or vasculitis diseases. A potential contribution of bipolar disorder and metabolic encephalopathies due to severe hypothyroidism, glucocorticoid treatment, accelerated thyroid hormone replacement therapy, or vitamin B deficiency is critically discussed. Another special feature of this case report is the linkage of HE to an autoimmune polyendocrine syndrome (type 3B) affecting the gastroduodenum in addition to the thyroid gland.
Process to Improve the Adherences of Copper to a PTFE Plate
Authors: Pérez Abel , Torres Alfonso , Torres Reydezel
Published: September 2016

A simple low plasma power and roughness free process for improving the adherence of Cu to PTFE is presented. The results show that low pressure and Ar flow combination are the drivers of this improved adherence. Copper Peel Strength Tensile values up to 60 kg/m are obtained which are comparable to those shown in commercial composite dielectrics for high-frequency applications Printed Circuit Boards.
Direct Comparison of19F qNMR and1H qNMR by Characterizing Atorvastatin Calcium Content
Authors: Liu Yang , Liu Zhaoxia , Yang Huaxin , He Lan
Published: September 2016

Quantitative nuclear magnetic resonance (qNMR) is a powerful tool in measuring drug content because of its high speed, sensitivity, and precision. Most of the reports were based on proton qNMR (1H qNMR) and only a few fluorine qNMR (19F qNMR) were reported. No research has been conducted to directly compare the advantage and disadvantage between these two methods. In the present study, both19F and1H qNMR were performed to characterize the content of atorvastatin calcium with the same internal standard. Linearity, precision, and results from two methods were compared. Results showed that19F qNMR has similar precision and sensitivity to1H qNMR. Both methods generate similar results compared to mass balance method. Major advantage from19F qNMR is that the analyte signal is with less or no interference from impurities.19F qNMR is an excellent approach to quantify fluorine-containing analytes.
SP600125 Attenuates Nicotine-Related Aortic Aneurysm Formation by Inhibiting Matrix Metalloproteinase Production and CC Chemokine-Mediated Macrophage Migration
Authors: Guo Zhen-Zhen , Cao Qun-An , Li Zong-Zhuang , Liu Li-Ping , Zhang Zhi , Zhu Ya-Juan , Chu Guang , Dai Qiu-Yan
Published: September 2016

Nicotine, a major chemical component of cigarettes, plays a pivotal role in the development of abdominal aortic aneurysm (AAA). c-Jun N-terminal kinase (JNK) has been demonstrated to participate in elastase-induced AAA. This study aimed to elucidate whether the JNK inhibitor SP600125 can attenuate nicotine plus angiotensin II- (AngII-) induced AAA formation and to assess the underlying molecular mechanisms. SP600125 significantly attenuated nicotine plus AngII-induced AAA formation. The expression of matrix metalloproteinase- (MMP-) 2, MMP-9, monocyte chemoattractant protein- (MCP-) 1, and regulated-on-activation, normal T-cells expressed and secreted (RANTES) was significantly upregulated in aortic aneurysm lesions but inhibited by SP600125.In vitro, nicotine induced the expression of MCP-1 and RANTES in both RAW264.7 (mouse macrophage) and MOVAS (mouse vascular smooth muscle) cells in a dose-dependent manner; expression was upregulated by 0.5 ng/mL nicotine but strongly downregulated by 500 ng/mL nicotine. SP600125 attenuated the upregulation of MCP-1 and RANTES expression and subsequent macrophage migration. In conclusion, SP600125 attenuates nicotine plus AngII-induced AAA formation likely by inhibiting MMP-2, MMP-9, MCP-1, and RANTES. The expression of chemokines in MOVAS cells induced by nicotine has an effect on RAW264.7 migration, which is likely to contribute to the development of nicotine-related AAA.
Impact of Recipient and Donor Obesity Match on the Outcomes of Liver Transplantation: All Matches Are Not Perfect
Authors: Beal Eliza W. , Tumin Dmitry , Conteh Lanla F. , Hanje A. James , Michaels Anthony J. , Hayes Don , Black Sylvester M. , Mumtaz Khalid
Published: September 2016

There is a paucity of literature examining recipient-donor obesity matching on liver transplantation outcomes. The United Network for Organ Sharing database was queried for first-time recipients of liver transplant whose age was ≥18 between January 2003 and September 2013. Outcomes including patient and graft survival at 30 days, 1 year, and 5 years and overall, liver retransplantation, and length of stay were compared between nonobese recipients receiving a graft from nonobese donors and obese recipient-obese donor, obese recipient-nonobese donor, and nonobese recipient-obese donor pairs. 51,556 LT recipients were identified, including 34,217 (66%) nonobese and 17,339 (34%) obese recipients. The proportions of patients receiving an allograft from an obese donor were 24% and 29%, respectively, among nonobese and obese recipients. Graft loss (HR: 1.27; 95% CI: 1.09–1.46;p=0.002) and mortality (HR: 1.38; 95% CI: 1.16–1.65;p<0.001) at 30 days were increased in the obese recipient-obese donor pair. However, 1-year graft (HR: 0.83; 95% CI: 0.74–0.93;p=0.002) and patient (HR: 0.84; 95% CI: 0.74–0.95;p=0.007) survival and overall patient (HR: 0.93; 95% CI: 0.86–1.00;p=0.042) survival were favorable. There is evidence of recipient and donor obesity disadvantage early, but survival curves demonstrate improved long-term outcomes. It is important to consider obesity in the donor-recipient match.