bluuebunny/crossref_metadata_2025 huggingface dataset:
Alumni‐based evaluation of a novel veterinary curriculum: are Nottingham graduates prepared for clinical practice?
Authors: Cobb K. A. , Brown G. A. , Hammond R. H. , Mossop L. H.
Published: August 2015

Introduction

Outcomes‐based education has been the core of the curriculum strategy of the Nottingham School of Veterinary Medicine and Science (SVMS) since its inception in 2006. As part of the ongoing curriculum evaluation, the first two graduating cohorts were invited to provide an appraisal of their preparation by the SVMS curriculum for their role in clinical practice. This paper provides brief accounts of the SVMS curriculum model, the development of the evaluation instrument and the findings of the alumni survey.

Materials and Methods

The evaluation instrument contained 25 attributes expected of SVMS graduates. Alumni rated their preparation for practice in relation to each attribute.

Results

The four highest rated characteristics were compassion for animals and the application of ethics to animal welfare; communication skills; recognising own limitations and seeking help and advice where needed and clinical examination skills. The four lowest rated were clinical case management and therapeutic strategies; dealing with veterinary public health and zoonotic issues; knowledge of current veterinary legislation and dealing with emergency and critical care cases. Free text responses were in line with these quantitative findings.

Conclusion

The results indicate that this sample of SVMS graduates were satisfied with their undergraduate education and felt well prepared for their role in clinical practice.
Genotyping and characterisation of the secretory lipolytic enzymes of Malassezia pachydermatis isolates collected from dogs
Authors: Teramoto Hideshi , Kumeda Yuko , Yokoigawa Kumio , Hosomi Koji , Kozaki Shunji , Mukamoto Masafumi , Kohda Tomoko
Published: August 2015

Introduction

Malassezia species are commensals of normal skin microbial flora of humans and animals. These may become pathogenic under certain conditions such as those associated with atopic dermatitis or otitis externa in dogs.

Material and methods

Isolates of Malassezia pachydermatis were obtained from 27 dogs with healthy external ears and 32 dogs with otitis externa. Isolates were characterised on the basis of their first internal transcribed spacer (ITS) and internal spacer 1 (IGS1) sequences. Their extracellular lipase and phospholipase activity were also analysed. Three types of phospholipase inhibitor were used to identify the subclasses of phospholipase associated with otitis externa.

Results

The clinical isolates were classified into three ITS and three IGS1 sequence types. No significant differences in pathogenicity were detected among the ITS or IGS1 genotypes, and all of the isolates exhibited similar levels of lipase activity. The isolates derived from the dogs with otitis externa showed significantly higher phospholipase activity than those obtained from the dogs with healthy external ears. A phospholipase D inhibitor reduced the phospholipase activity of the isolates obtained from the dogs with otitis externa.

Conclusions

This study did not show any significant differences in pathogenicity among the ITS or IGS1 genotypes but does suggest that phospholipase D might be one of the virulence factors involved in the inflammation of the external ear caused by M. pachydermatis.
Acceptance and effects of a therapeutic renal food in pet cats with chronic kidney disease
Authors: Fritsch Dale A , Jewell Dennis E , Leventhal P S , Brejda J , Ahle N W , Schiefelbein H M , Forrester S D
Published: August 2015

Introduction

Renal foods are used to manage chronic kidney disease (CKD) in dogs and cats, but their effectiveness may be limited by the ability to transition animals to them.

Material and Methods

In a prospective study, pet cats with previously undiagnosed kidney disease (20 International Renal Interest Society (IRIS) 1, 61 IRIS 2, 14 IRIS 3/4, 33 at risk for CKD) were transitioned to a renal food. Markers of renal function were measured and owners answered questionnaires about their pet over one year.

Results

All but eight cats (120/128; 94 per cent) successfully transitioned to the renal food. Most of the time, cats moderately or extremely liked the food (89 per cent), ate at least half (73 per cent) and were moderately or extremely enthusiastic while eating (68 per cent). Cats rarely disliked the food (2 per cent) or refused to eat it (1 per cent). Markers of renal function were unchanged in IRIS 1 and 2 cats and changed little in IRIS 3/4 cats. In all groups, owner‐assessed quality of life improved initially and then remained stable. Mean bodyweight did not change in cats with CKD.

Conclusions

Most cats with CKD successfully transitioned to the renal food. The results also support previous studies that the renal food can help stabilise cats with CKD.
The role of gluconate production by Pseudomonas spp. in the mineralization and bioavailability of calcium–phytate to Nicotiana tabacum
Authors: Giles Courtney D. , Hsu Pei-Chun (Lisa) , Richardson Alan E. , Hurst Mark R.H. , Hill Jane E.
Published: August 2015

Organic phosphorus (P) is abundant in most soils but is largely unavailable to plants. Pseudomonas spp. can improve the availability of P to plants through the production of phytases and organic anions. Gluconate is a major component of Pseudomonas organic anion production and may therefore play an important role in the mineralization of insoluble organic P forms such as calcium–phytate (CaIHP). Organic anion and phytase production was characterized in 2 Pseudomonas spp. soil isolates (CCAR59, Ha200) and an isogenic mutant of strain Ha200, which lacked a functional glucose dehydrogenase (Gcd) gene (strain Ha200 gcd::Tn5B8). Wild-type and mutant strains of Pseudomonas spp. were evaluated for their ability to solubilize and hydrolyze CaIHP and to promote the growth and assimilation of P by tobacco plants. Gluconate, 2-keto-gluconate, pyruvate, ascorbate, acetate, and formate were detected in Pseudomonas spp. supernatants. Wild-type pseudomonads containing a functional gcd could produce gluconate and mineralize CaIHP, whereas the isogenic mutant could not. Inoculation with Pseudomonas improved the bioavailability of CaIHP to tobacco plants, but there was no difference in plant growth response due to Gcd function. Gcd function is required for the mineralization of CaIHP in vitro; however, further studies will be needed to quantify the relative contribution of specific organic anions such as gluconate to plant growth promotion by soil pseudomonads.
Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance
Authors: Holman Devin B. , Chénier Martin R.
Published: August 2015

Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota.
Limits of imagination: the 150th Anniversary of Mendel’s Laws, and why Mendel failed to see the importance of his discovery for Darwin’s theory of evolution
Authors: Singh Rama S.
Published: August 2015

Mendel is credited for discovering Laws of Heredity, but his work has come under criticism on three grounds: for possible falsification of data to fit his expectations, for getting undue credit for the laws of heredity without having ideas of segregation and independent assortment, and for being interested in the development of hybrids rather than in the laws of heredity. I present a brief review of these criticisms and conclude that Mendel deserved to be called the father of genetics even if he may not, and most likely did not, have clear ideas of segregation and particulate determiners as we know them now. I argue that neither Mendel understood the evolutionary significance of his findings for the problem of genetic variation, nor would Darwin have understood their significance had he read Mendel’s paper. I argue that the limits to imagination, in both cases, came from their mental framework being shaped by existing paradigms—blending inheritance in the case of Darwin, hybrid development in the case of Mendel. Like Einstein, Darwin’s natural selection was deterministic; like Niels Bohr, Mendel’s Laws were probabilistic—based on random segregation of trait-determining “factors”. Unlike Einstein who understood quantum mechanics, Darwin would have been at a loss with Mendel’s paper with no guide to turn to. Geniuses in their imaginations are like heat-seeking missiles locked-in with their targets of deep interests and they generally see things in one dimension only. Imagination has limits; unaided imagination is like a bird without wings — it goes nowhere.
Vibration and Acoustic Responses of an Orthotropic Composite Conical Shell in a Hygroscopic Environment
Authors: Zhao Xin , Li Yueming
Published: August 2015

The vibration and acoustic radiation for an orthotropic composite conical shell in a hygroscopic environment are explored through the wave propagation approach and Galerkin method. Theoretical results of the natural vibration and far field sound pressure are presented with incremental moisture content. The effects of incremental stiffness and different semi-vertex angle on the acoustic radiation characteristics are studied too. It is found that the natural frequencies decrease with incremental moisture content. The wavenumbers associated with the lowest frequency mode reaches the modal indices corresponding to the lowest buckling mode near the critical buckling moisture content. With the increasing moisture content, a shifting of natural frequencies toward lower frequency band could be observed in lower frequency band of the modal density in constant frequency band. The overall sound pressure level (SPL) decreases generally with the moisture content, but shows a marginal increase near the critical buckling moisture content. The modal density and overall SPL decrease with the incremental stiffness generally, which increases with the decrease of the semi-vertex angle.
A note on compact elements of the lattice of solubly saturated formations
Authors: Vorob’ev Nikolay N.
Published: August 2015

It is proved that every [Formula: see text]-closed solubly saturated formation contained in a compact element of the lattice of all [Formula: see text]-closed saturated formations of finite groups is also contained in some compact element of the lattice of all [Formula: see text]-closed solubly saturated formations of finite groups.
Magnetotelluric imaging integrated with seismic, gravity, magnetic and well-log data for basement and carbonate reservoir mapping in the São Francisco Basin, Brazil
Authors: Solon F. F. , Fontes S. L. , Meju M. A.
Published: August 2015

We evaluate the use of the magnetotelluric (MT) method to locate crystalline basement and overlying carbonate reservoir rocks underneath a thick overburden in the São Francisco basin in Brazil. Mapping the complex basement and the carbonate reservoir using seismic reflection is a major problem in hydrocarbon exploration in this intracratonic basin, and it is expected that MT will provide useful complementary information. In the present study, we analysed 31 MT soundings along four survey lines in the central region of the basin. The MT soundings covered a period range of 0.001–100 s, probing the subsurface resistivity structure down to a maximum depth of about 15 km. The MT data were inverted using a regularized two-dimensional (2D) inversion algorithm with a variety of
a priori
data for comparison. For model appraisal, we analysed well log (gamma ray, deep resistivity and neutron porosity) data as well as seismic, gravity and magnetic profiles coincident with one MT line passing through the well. We found that shallow geological boundaries separating zones of strong resistivity contrasts also coincide with seismic boundaries in the inversion models with or without a priori data. Using gravity data, it was also possible to define the compartmentalized basement in this sector of São Francisco Basin, not clear in the seismic section. However, only by integrating all available information were we able to map the Lagoa do Jacaré and Sete Lagoas carbonate member-formations of the Bambuí Group, which are considered to host both the source and reservoir rocks identified from past exploratory history of this basin. We also imaged a basement structural high with thinned or disrupted conductive cover rocks over a known zone of hydrocarbon microseepage and a buried conductive (source rock?) channel at its NW margin, the trace of which coincides with the present-day River Paracatu along which gas bubbles have been observed. This suggests that MT may be fruitfully integrated with gravity, magnetic and seismic data to study the structural controls on hydrocarbon occurrence in this basin.
Stochastic structural modelling in sparse data situations
Authors: Cherpeau Nicolas , Caumon Guillaume
Published: August 2015

This paper introduces a stochastic structural modelling method that honours interpretations of both faults and stratigraphic horizons on maps and cross-sections in conjunction with prior information, such as fault orientation and statistical size–displacement relationships. The generated stochastic models sample not only geometric uncertainty but also topological uncertainty about the fault network. Faults are simulated sequentially; at each step, fault traces are randomly chosen to constrain a fault surface in order to obtain consistent fault geometry and displacement profile. For each simulated fault network, stratigraphic modelling is performed to honour interpreted horizons using an implicit approach. Geometrical uncertainty on stratigraphic horizons can then be simulated by adding a correlated random noise to the stratigraphic scalar field. This strategy automatically maintains the continuity between faults and horizons.

The method is applied to a Middle East field where stochastic structural models are generated from interpreted two-dimensional (2D) seismic lines, first by representing only stratigraphic uncertainty and then by adding uncertainty about the fault network. These two scenarios are compared in terms of gross rock volume (GRV) uncertainty and show a significant increase in GRV uncertainty when fault uncertainties are considered. This underlines the key role of faults in resource estimation uncertainties and advocates a more systematic fault uncertainty consideration in subsurface studies, especially in settings in which the data are sparse.
Application of experimental design to estimate hydrocarbons initially in place
Authors: Imrie C. E. , Macrae E. J.
Published: August 2015

When assessing a reservoir’s Hydrocarbon Initially In Place (HIIP) volumes there are often many uncertain input factors. If they are discretized into low, mid and high case scenarios, this can result in tens of thousands of possible combinations of factors and it is often necessary to reduce the amount of uncertain factors to a manageable number. This can reduce the range of model outcomes, and the confidence in the predicted volumes will be overestimated. Experimental design allows a reduced representative set of models to be constructed for uncertainty analysis when it would take too long to construct all possible realizations. This paper uses a case study to demonstrate a refined application of experimental design, whereby uncertain factors were first identified and experts were consulted to specify high, mid and low values with associated probabilities. The analysis was completed in two parts: a screening phase, whereby non-significant factors were eliminated; and an optimization phase, whereby a limited number of model runs were used to train a proxy model for use in a Monte Carlo procedure to generate a probability distribution of HIIP. The key advantage of the method is the comprehensive treatment of uncertainty with a reduced amount of modelling effort.
Geochemical characterization of oils and their source rocks in the Barmer Basin, Rajasthan, India
Authors: Farrimond Paul , Naidu Bodapati S. , Burley Stuart D. , Dolson John , Whiteley Nicholas , Kothari Vachaspati
Published: August 2015

The Barmer Basin is a failed continental rift of late Cretaceous–Eocene age in Rajasthan, NW India, containing prolific hydrocarbon resources, with 33 discoveries having been made in the last decade. The basin is predominantly oil-prone, although gas discoveries have been made in the deeper parts of the basin. Oils in the Barmer Basin are highly waxy, a result of the lacustrine nature of the source rocks that dominate the sedimentary fill of the basin. Detailed interpretation of the molecular composition of the oils defines three main oil groups that can be related to differing sources. The oils are all distinctively lacustrine in origin, although differing in specific source-facies characteristics. All of the oils are isotopically light, mostly in the −29‰ to −33‰ range.

Most oils in the northern Barmer Basin (groups 1A and 1B) are interpreted to have been generated from the Late Paleocene Barmer Hill Formation, an excellent oil-prone source rock with predominantly Type I lacustrine algal and bacterial kerogen. Group 2 oils are subordinate in abundance, occurring only in the southern part of the basin, and are interpreted to be at least partly sourced from the overlying Early Eocene Dharvi Dungar Formation, which is characterized by mixed Type I and Type III kerogen, and attains oil maturity only in the southern basin. Group 3 oils are less common, and are of higher maturity than the Group 1 oils, but also appear to have been generated from the Barmer Hill Formation where it was buried more deeply in the central and southern parts of the basin. However, recognition of probable Mesozoic sediments in sub-basins beneath the Tertiary Barmer Basin introduces a further source-rock candidate for the Group 3 oils. A high maturity hydrocarbon charge that is recognized in the gasoline-range hydrocarbons in the Group 2 oils of the southern Barmer Basin may also be from a Mesozoic source rock, or from the Barmer Hill Formation that is much more deeply buried in this part of the basin than in the north, and represents a more mixed oil- and gas-prone source.
The Mull Paleocene dykes: some insights into the nature of major dyke swarms
Authors: Macdonald R. , Fettes D.J. , Bagiński B.
Published: August 2015

At about 1000 km long and with a magmatic volume exceeding 850 km
3
, the Paleocene Mull Dyke Swarm qualifies as a giant dyke swarm. As such, it offers important insights into the nature of such swarms. Magma flowage laterally from the Mull Central Complex is supported by evidence of recent magma flowage in rift-related volcanic areas. Conduits were frequently used by more than one magma pulse at different times. Pre-heating of conduits by basaltic magma enabled salic magmas to propagate for >400 km from Mull. The Southern Upland Fault had a major influence on dyke propagation in the southern sector of the swarm, variably arresting magma migration or diverting magma vertically or laterally, in one case for 16 km laterally. A significant role for crustal heterogeneity in controlling dyke dynamics is advocated. Recent models point to important interactions between the dykes and adjacent Paleocene central complexes. The dyke swarm can potentially contribute significant information on the evolution of the Mull plumbing system, such as the formation of compositional zoning and the role of magma input in chamber rupture.
Synchronic Versus Diachronic Explanation and the Nature of the Language Faculty
Authors: Anderson Stephen R.
Published: August 2015

The nineteenth-century conception that linguistic structure was to be explained by recourse to the histories of languages was largely abandoned with the rise of synchronic theories in the twentieth century, but has recently returned to prominence. Whereas traditional generative theories of language have tended to attribute crosslinguistic regularities to constraints imposed on the class of possible grammars by the human Language Faculty, some scholars have argued that this is often a mistake: that there are no (or at least very few) real substantive universals of language, and that the regularities in question arise from common paths of diachronic change having their basis in factors outside of the defining properties of the set of cognitively accessible grammars. This review surveys evidence for that position, primarily in phonology but also in morphology and syntax. I argue that in phonology, there are at present no convincingly demonstrated substantive universals governing the set of possible regularities, and that the generalizations we find should be attributed to a combination of contingent historical developments and biases in the learning algorithm that relates available data to the grammars learners acquire. In morphology and syntax, I argue that some apparent generalizations are indeed the product of diachronic change rather than synchronic constraint.
Iron-induced reactive oxygen species mediate transporter DMT1 endocytosis and iron uptake in intestinal epithelial cells
Authors: Esparza Andrés , Gerdtzen Ziomara P. , Olivera-Nappa Alvaro , Salgado J. Cristian , Núñez Marco T.
Published: August 2015

Recent evidence shows that iron induces the endocytosis of the iron transporter dimetal transporter 1 (DMT1) during intestinal absorption. We, and others, have proposed that iron-induced DMT1 internalization underlies the mucosal block phenomena, a regulatory response that downregulates intestinal iron uptake after a large oral dose of iron. In this work, we investigated the participation of reactive oxygen species (ROS) in the establishment of this response. By means of selective surface protein biotinylation of polarized Caco-2 cells, we determined the kinetics of DMT1 internalization from the apical membrane after an iron challenge. The initial decrease in DMT1 levels in the apical membrane induced by iron was followed at later times by increased levels of DMT1. Addition of Fe2+, but not of Cd2+, Zn2+, Cu2+, or Cu1+, induced the production of intracellular ROS, as detected by 2′,7′-dichlorofluorescein (DCF) fluorescence. Preincubation with the antioxidant N-acetyl-l-cysteine (NAC) resulted in increased DMT1 at the apical membrane before and after addition of iron. Similarly, preincubation with the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) resulted in the enhanced presence of DMT1 at the apical membrane. The decrease of DMT1 levels at the apical membrane induced by iron was associated with decreased iron uptake rates. A kinetic mathematical model based on operational rate constants of DMT1 endocytosis and exocytosis is proposed. The model qualitatively captures the experimental observations and accurately describes the effect of iron, NAC, and DMSO on the apical distribution of DMT1. Taken together, our data suggest that iron uptake induces the production of ROS, which modify DMT1 endocytic cycling, thus changing the iron transport activity at the apical membrane.
Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries
Authors: Rutkai Ibolya , Dutta Somhrita , Katakam Prasad V. , Busija David W.
Published: August 2015

Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using Nω-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I–V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury.
Angiopoietin-1 prevents severe bleeding complications induced by heparin-like drugs and fibroblast growth factor-2 in mice
Authors: Jerebtsova Marina , Das Jharna R. , Tang Pingtao , Wong Edward , Ray Patricio E.
Published: August 2015

Critically ill children can develop bleeding complications when treated with heparin-like drugs. These events are usually attributed to the anticoagulant activity of these drugs. However, previous studies showed that fibroblast growth factor-2 (FGF-2), a heparin-binding growth factor released in the circulation of these patients, could precipitate intestinal hemorrhages in mice treated with the heparin-like drug pentosan polysulfate (PPS). Yet very little is known about how FGF-2 induces bleeding complications in combination with heparin-like drugs. Here, we examined the mechanisms by which circulating FGF-2 induces intestinal hemorrhages in mice treated with PPS. We used a well-characterized mouse model of intestinal hemorrhages induced by FGF-2 plus PPS. Adult FVB/N mice were infected with adenovirus carrying Lac-Z or a secreted form of recombinant human FGF-2, and injected with PPS, at doses that do not induce bleeding complications per se. Mice treated with FGF-2 in combination with PPS developed an intestinal inflammatory reaction that increased the permeability and disrupted the integrity of submucosal intestinal vessels. These changes, together with the anticoagulant activity of PPS, induced lethal hemorrhages. Moreover, a genetically modified form of the endothelial ligand angiopoietin-1 (Ang-1*), which has powerful antipermeability and anti-inflammatory activity, prevented the lethal bleeding complications without correcting the anticoagulant status of these mice. These findings define new mechanisms through which FGF-2 and Ang-1* modulate the outcome of intestinal bleeding complications induced by PPS in mice and may have wider clinical implications for critically ill children treated with heparin-like drugs.
Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction
Authors: Beaumont Eric , Southerland Elizabeth M. , Hardwick Jean C. , Wright Gary L. , Ryan Shannon , Li Ying , KenKnight Bruce H. , Armour J. Andrew , Ardell Jeffrey L.
Published: August 2015

This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls ( n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% ( P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% ( P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls ( P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls ( P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls ( P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein ( P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.
Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation
Authors: Lucitti Jennifer L. , Tarte Natalie J. , Faber James E.
Published: August 2015

The number and diameter of native collaterals in tissues of healthy mice vary widely, resulting in large differences in tissue injury in occlusive diseases. Recent studies suggest similar variation may exist in humans. Collateral variation in mice is determined by genetic background-dependent differences in embryonic collateral formation, by variation in maturation of the nascent collaterals, and by environmental factors such as aging that cause collateral rarefaction in the adult. Recently, formation of the collateral circulation in the brain was found to involve a unique VEGF-A-dependent “arteriolar” angiogenic sprouting-like mechanism. Elsewhere, chloride intracellular protein 4 (CLIC4) was implicated but not investigated directly, prompting the present study. Deletion of Clic4 had no effect on embryonic collaterogenesis. However, during collateral maturation from embryonic day 18.5 to postnatal day 7, reduced mural cell investment was observed and excessive pruning of collaterals occurred. Growth in collateral diameter was reduced. This resulted in 50% fewer collaterals of smaller diameter in the adult and thus larger infarct volume after middle cerebral artery occlusion. During collateral maturation, CLIC4 deficiency resulted in reduced expression of Vegfr2, Vegfr1, Vegfc, and mural cell markers, but not notch-pathway genes. Overexpression of VEGF-A in Clic4−/−mice had no effect on collaterogenesis, but rescued the above defects in collateral maturation by preventing mural cell loss and collateral pruning, thus restoring collateral number and diameter and reducing stroke severity in the adult. CLIC4 is not required for collaterogenesis but is essential for perinatal maturation of nascent collaterals through a mechanism that supports VEGF signaling.
Mitochondrial flash as a novel biomarker of mitochondrial respiration in the heart
Authors: Gong Guohua , Liu Xiaoyun , Zhang Huiliang , Sheu Shey-Shing , Wang Wang
Published: August 2015

Mitochondrial respiration through electron transport chain (ETC) activity generates ATP and reactive oxygen species in eukaryotic cells. The modulation of mitochondrial respiration in vivo or under physiological conditions remains elusive largely due to the lack of appropriate approach to monitor ETC activity in a real-time manner. Here, we show that ETC-coupled mitochondrial flash is a novel biomarker for monitoring mitochondrial respiration under pathophysiological conditions in cultured adult cardiac myocyte and perfused beating heart. Through real-time confocal imaging, we follow the frequency of a transient bursting fluorescent signal, named mitochondrial flash, from individual mitochondria within intact cells expressing a mitochondrial matrix-targeted probe, mt-cpYFP (mitochondrial-circularly permuted yellow fluorescent protein). This mt-cpYFP recorded mitochondrial flash has been shown to be composed of a major superoxide signal with a minor alkalization signal within the mitochondrial matrix. Through manipulating physiological substrates for mitochondrial respiration, we find a close coupling between flash frequency and the ETC electron flow, as measured by oxygen consumption rate in cardiac myocyte. Stimulating electron flow under physiological conditions increases flash frequency. On the other hand, partially block or slowdown electron flow by inhibiting the F0F1ATPase, which represents a pathological condition, transiently increases then decreases flash frequency. Limiting electron entrance at complex I by knocking out Ndufs4, an assembling subunit of complex I, suppresses mitochondrial flash activity. These results suggest that mitochondrial electron flow can be monitored by real-time imaging of mitochondrial flash. The mitochondrial flash frequency could be used as a novel biomarker for mitochondrial respiration under physiological and pathological conditions.
Perspectives on edema in childhood nephrotic syndrome
Authors: Teoh Chia Wei , Robinson Lisa A. , Noone Damien
Published: August 2015

There have been two major theories surrounding the development of edema in nephrotic syndrome (NS), namely, the under- and overfill hypotheses. Edema is one of the cardinal features of NS and remains one of the principal reasons for admission of children to the hospital. Recently, the discovery that proteases in the glomerular filtrate of patients with NS are activating the epithelial sodium channel (ENaC), resulting in intrarenal salt retention and thereby contributing to edema, might suggest that targeting ENaC with amiloride might be a suitable strategy to manage the edema of NS. Other potential agents, particularly urearetics and aquaretics, might also prove useful in NS. Recent evidence also suggests that there may be other areas involved in salt storage, especially the skin, and it will be intriguing to study the implications of this in NS.
Effect of hypertension and carotid occlusion on brain parenchymal arteriole structure and reactivity
Authors: Sweet Julie G. , Chan Siu-Lung , Cipolla Marilyn J.
Published: August 2015

We studied the effect of hypertension and chronic hypoperfusion on brain parenchymal arteriole (PA) structure and function. PAs were studied isolated and pressurized from 18-wk-old Wistar-Kyoto (WKY18; n = 8) and spontaneously hypertensive stroke prone (SHRSP18; n = 8) and 5-wk-old prehypertensive (SHRSP5; n = 8) rats. In separate groups, unilateral common carotid artery occlusion (UCCAo) was performed for 4 wk to cause chronic hypoperfusion in 18-wk-old WKY (WKY18-CH; n = 8) and SHRSP (SHRSP18-CH; n = 8). UCCAo caused PAs to have significantly diminished myogenic tone (31 ± 3 vs. 14 ± 6% at 60 mmHg; P < 0.05) and reactivity to pressure from WKY18-CH vs. WKY18 animals. The effect of UCCAo was limited to normotensive animals, as there was little effect of chronic hypoperfusion on vascular reactivity or percent tone in PAs from SHRSP18 vs. SHRSP18-CH animals (53 ± 4 vs. 41 ± 3%; P > 0.05). However, PAs from SHRSP18 and SHRSP5 animals had significantly greater tone compared with WKY18, suggesting an effect of strain and not hypertension per se on PA vasoconstriction. Structurally, PAs from SHRSP18 and SHRSP5 animals had similar sized lumen diameters, but increased wall thickness and distensibility compared with WKY18. Interestingly, chronic hypoperfusion did not affect the structure of PAs from either WKY18-CH or SHRSP18-CH animals. Thus PAs responded to UCCAo with active vasodilation, but not structural remodeling, an effect that was absent in SHRSP. The increased tone of PAs from SHRSP animals, combined with lack of response to chronic hypoperfusion, may contribute to the propensity for ischemic lesions and increased perfusion deficit during hypertension.
The effects of age and resistance loading on skeletal muscle ribosome biogenesis
Authors: Stec Michael J. , Mayhew David L. , Bamman Marcas M.
Published: August 2015

The hypertrophic response to resistance training is generally attenuated with aging; yet the mechanisms regulating this phenomenon are largely unknown. Several studies to date have shown blunted translational efficiency following acute resistance exercise in older adults; however, the effects on translational capacity (i.e., ribosome biogenesis) have not yet been examined. Thus the purpose of this study was to examine changes in markers of ribosome biogenesis following an acute bout of resistance loading (RL; 9 sets × 10 repetitions of knee extensions) in younger (Y; n = 14; 39.2 ± 4.1 yr) and older (O; n = 12; 75.7 ± 5.7 yr) adults. Vastus lateralis biopsies were taken pre- and 24 h post-RL, and muscle samples were analyzed for total RNA content, 45S pre-rRNA expression, ribosomal protein content, and levels of signaling proteins that regulate ribosome biogenesis. Before RL, O had higher total RNA content (+28%; P < 0.05), a trend toward higher 45S pre-rRNA expression (+59%; P = 0.08), and greater protein content of several ribosomal components (≈ +50–80%; P < 0.05) than Y. However, 24 h post-RL, only Y increased 45S pre-rRNA expression (+34%; P < 0.01), possibly driven by higher basal p-Rb (Ser780) (+61%; P = 0.10), and a robust transcription initiation factor (TIF)-1a response (+75%; P < 0.05). RL tended to increase protein components of the 40S ribosomal subunit in Y only (≈ +20–25%; P ≤ 0.12). Overall, the data suggest blunted ribosome biogenesis in response to RL in O, which may be a potential mechanism driving the age-related attenuation of resistance training-induced hypertrophy.
Online NIR Analysis and Prediction Model for Synthesis Process of Ethyl 2-Chloropropionate
Authors: Zhang Wei , Song Hang , Lu Jing , Liu Wen , Nie Lirong , Yao Shun
Published: August 2015

Online near-infrared spectroscopy was used as a process analysis technique in the synthesis of 2-chloropropionate for the first time. Then, the partial least squares regression (PLSR) quantitative model of the product solution concentration was established and optimized. Correlation coefficient (R2) of partial least squares regression (PLSR) calibration model was 0.9944, and the root mean square error of correction (RMSEC) was 0.018105 mol/L. These values of PLSR and RMSEC could prove that the quantitative calibration model had good performance. Moreover, the root mean square error of prediction (RMSEP) of validation set was 0.036429 mol/L. The results were very similar to those of offline gas chromatographic analysis, which could prove the method was valid.
Neural Plasticity in Common Forms of Chronic Headaches
Authors: Lai Tzu-Hsien , Protsenko Ekaterina , Cheng Yu-Chen , Loggia Marco L. , Coppola Gianluca , Chen Wei-Ta
Published: August 2015

Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache.
Fractal Analysis and the Diagnostic Usefulness of Silver Staining Nucleolar Organizer Regions in Prostate Adenocarcinoma
Authors: Stepan Alex , Simionescu Cristiana , Pirici Daniel , Ciurea Raluca , Margaritescu Claudiu
Published: August 2015

Pathological diagnosis of prostate adenocarcinoma often requires complementary methods. On prostate biopsy tissue from 39 patients including benign nodular hyperplasia (BNH), atypical adenomatous hyperplasia (AAH), and adenocarcinomas, we have performed combined histochemical-immunohistochemical stainings for argyrophilic nucleolar organizer regions (AgNORs) and glandular basal cells. After ascertaining the pathology, we have analyzed the number, roundness, area, and fractal dimension of individual AgNORs or of their skeleton-filtered maps. We have optimized here for the first time a combination of AgNOR morphological denominators that would reflect best the differences between these pathologies. The analysis of AgNORs’ roundness, averaged from large composite images, revealed clear-cut lower values in adenocarcinomas compared to benign and atypical lesions but with no differences between different Gleason scores. Fractal dimension (FD) of AgNOR silhouettes not only revealed significant lower values for global cancer images compared to AAH and BNH images, but was also able to differentiate between Gleason pattern 2 and Gleason patterns 3–5 adenocarcinomas. Plotting the frequency distribution of the FDs for different pathologies showed clear differences between all Gleason patterns and BNH. Together with existing morphological classifiers, AgNOR analysis might contribute to a faster and more reliable machine-assisted screening of prostatic adenocarcinoma, as an essential aid for pathologists.
Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice
Authors: Nakajima Kenichi , Mita Tomoya , Osonoi Yusuke , Azuma Kosuke , Takasu Toshiyuki , Fujitani Yoshio , Watada Hirotaka
Published: August 2015

Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E-deficient mice.
The Influence of Urinary Concentrations of Organophosphate Metabolites on the Relationship between BMI and Cardiometabolic Health Risk
Authors: Ranjbar Mahsa , Rotondi Michael A. , Ardern Chris I. , Kuk Jennifer L.
Published: August 2015

The objective was to determine whether detectable levels of OP metabolites influence the relationship between BMI and cardiometabolic health. This cross-sectional study was conducted using 2227 adults from the 1999–2008 NHANES datasets. Urinary concentrations of six dialkyl phosphate metabolites were dichotomized to above and below the detection limit. Weighted multiple regression analysis was performed adjusting for confounding variables. Independent of BMI, individuals with detectable metabolites had higher diastolic blood pressure (for dimethylphosphate, diethylphosphate, and diethyldithiophosphate;P<0.05), lower HDL (for diethyldithiophosphate;P=0.02), and higher triglyceride (for dimethyldithiophosphate;P=0.05) than those below detection. Contrarily, those with detectable dimethylthiophosphate had better LDL, HDL, and total cholesterol, independent of BMI. Individuals at a higher BMI range who had detectable diethylphosphate (interaction:P=0.03) and diethylthiophosphate (interaction:P=0.02) exhibited lower HDL, while little difference existed between OP metabolite detection statuses at lower BMIs. Similarly, individuals with high BMIs and detectable diethylphosphate had higher triglyceride than those without detectable levels, while minimal differences between diethylphosphate detection statuses were observed at lower BMIs (interaction:P=0.02). Thus, cardiometabolic health outcome differs depending on the specific OP metabolite being examined, with higher BMIs amplifying health risk.
Investigation of the Effect of Dimple Bionic Nonsmooth Surface on Tire Antihydroplaning
Authors: Zhou Haichao , Wang Guolin , Ding Yangmin , Yang Jian , Zhai Huihui
Published: August 2015

Inspired by the idea that bionic nonsmooth surfaces (BNSS) reduce fluid adhesion and resistance, the effect of dimple bionic nonsmooth structure arranged in tire circumferential grooves surface on antihydroplaning performance was investigated by using Computational Fluid Dynamics (CFD). The physical model of the object (model of dimple bionic nonsmooth surface distribution, hydroplaning model) and SSTk-ωturbulence model are established for numerical analysis of tire hydroplaning. By virtue of the orthogonal table L16(45), the parameters of dimple bionic nonsmooth structure design compared to the smooth structure were analyzed, and the priority level of the experimental factors as well as the best combination within the scope of the experiment was obtained. The simulation results show that dimple bionic nonsmooth structure can reduce water flow resistance by disturbing the eddy movement in boundary layers. Then, optimal type of dimple bionic nonsmooth structure is arranged on the bottom of tire circumferential grooves for hydroplaning performance analysis. The results show that the dimple bionic nonsmooth structure effectively decreases the tread hydrodynamic pressure when driving on water film and increases the tire hydroplaning velocity, thus improving tire antihydroplaning performance.