bluuebunny/crossref_metadata_2025 huggingface dataset:
A theoretical study of biological membrane response to temperature gradients at the single-cell level
Authors: Atia Lior , Givli Sefi
Published: March 2014

Recent experimental studies provide evidence for the existence of a spatially non-uniform temperature field in living cells and in particular in their plasma membrane. These findings have led to the development of a new and exciting field: thermal biology at the single-cell level. Here, we examine theoretically a specific aspect of this field, i.e. how temperature gradients at the single-cell level affect the phase behaviour and geometry of heterogeneous membranes. We address this issue by using the Onsager reciprocal relations combined with a simple model for a binary lipid mixture. We demonstrate that even small temperature variations along the membrane may introduce intriguing phenomena, such as phase separation above the critical temperature and unusual shape response. These results also suggest that the shape of a membrane can be manipulated by dynamically controlling the temperature field in its vicinity. The effects of intramembranous temperature gradients have never been studied experimentally. Thus, the predictions of the current contribution are of a somewhat speculative nature. Experimental verification of these results could mark the beginning of a new line of research in the field of biological membranes. We report our findings with the hope of inspiring others to perform such experiments.
Complex role of space in the crossing of fitness valleys by asexual populations
Authors: Komarova Natalia L. , Shahriyari Leili , Wodarz Dominik
Published: March 2014

The evolution of complex traits requires the accumulation of multiple mutations, which can be disadvantageous, neutral or advantageous relative to the wild-type. We study two spatial (two-dimensional) models of fitness valley crossing (the constant-population Moran process and the non-constant-population contact process), varying the number of loci involved and the degree of mixing. We find that spatial interactions accelerate the crossing of fitness valleys in the Moran process in the context of neutral and disadvantageous intermediate mutants because of the formation of mutant islands that increase the lifespan of mutant lineages. By contrast, in the contact process, spatial structure can accelerate or delay the emergence of the complex trait, and there can even be an optimal degree of mixing that maximizes the rate of evolution. For advantageous intermediate mutants, spatial interactions always delay the evolution of complex traits, in both the Moran and contact processes. The role of the mutant islands here is the opposite: instead of protecting, they constrict the growth of mutants. We conclude that the laws of population growth can be crucial for the effect of spatial interactions on the rate of evolution, and we relate the two processes explored here to different biological situations.
Hygroscopic swelling and shrinkage of latewood cell wall micropillars reveal ultrastructural anisotropy
Authors: Rafsanjani Ahmad , Stiefel Michael , Jefimovs Konstantins , Mokso Rajmund , Derome Dominique , Carmeliet Jan
Published: March 2014

We document the hygroscopic swelling and shrinkage of the central and the thickest secondary cell wall layer of wood (named S2) in response to changes in environmental humidity using synchrotron radiation-based phase contrast X-ray tomographic nanoscopy. The S2 layer is a natural fibre-reinforced nano-composite polymer and is strongly reactive to water. Using focused ion beam, micropillars with a cross section of few micrometres are fabricated from the S2 layer of the latewood cell walls of Norway spruce softwood. The thin neighbouring cell wall layers are removed to prevent hindering or restraining of moisture-induced deformation during swelling or shrinkage. The proposed experiment intended to get further insights into the microscopic origin of the anisotropic hygro-expansion of wood. It is found that the swelling/shrinkage strains are highly anisotropic in the transverse plane of the cell wall, larger in the normal than in the direction parallel to the cell wall's thickness. This ultrastructural anisotropy may be due to the concentric lamellation of the cellulose microfibrils as the role of the cellulose microfibril angle in the transverse swelling anisotropy is negligible. The volumetric swelling of the cell wall material is found to be substantially larger than the one of wood tissues within the growth ring and wood samples made of several growth rings. The hierarchical configuration in wood optimally increases its dimensional stability in response to a humid environment with higher scales of complexity.
A century of variation in the dependence of Greenland iceberg calving on ice sheet surface mass balance and regional climate change
Authors: Bigg G. R. , Wei H. L. , Wilton D. J. , Zhao Y. , Billings S. A. , Hanna E. , Kadirkamanathan V.
Published: March 2014

Iceberg calving is a major component of the total mass balance of the Greenland ice sheet (GrIS). A century-long record of Greenland icebergs comes from the International Ice Patrol's record of icebergs (I48N) passing latitude 48° N, off Newfoundland. I48N exhibits strong interannual variability, with a significant increase in amplitude over recent decades. In this study, we show, through a combination of nonlinear system identification and coupled ocean–iceberg modelling, that I48N's variability is predominantly caused by fluctuation in GrIS calving discharge rather than open ocean iceberg melting. We also demonstrate that the episodic variation in iceberg discharge is strongly linked to a nonlinear combination of recent changes in the surface mass balance (SMB) of the GrIS and regional atmospheric and oceanic climate variability, on the scale of the previous 1–3 years, with the dominant causal mechanism shifting between glaciological (SMB) and climatic (ocean temperature) over time. We suggest that this is a change in whether glacial run-off or under-ice melting is dominant, respectively. We also suggest that GrIS calving discharge is episodic on at least a regional scale and has recently been increasing significantly, largely as a result of west Greenland sources.
Evidence of social niche construction: persistent and repeated social interactions generate stronger personalities in a social spider
Authors: Laskowski Kate L. , Pruitt Jonathan N.
Published: March 2014

While there are now a number of theoretical models predicting how consistent individual differences in behaviour may be generated and maintained, so far, there are few empirical tests. The social niche specialization hypothesis predicts that repeated social interactions among individuals may generate among-individual differences and reinforce within-individual consistency through positive feedback mechanisms. Here, we test this hypothesis using groups of the social spiderStegodyphus mimosarumthat differ in their level of familiarity. In support of the social niche specialization hypothesis, individuals in groups of spiders that were more familiar with each other showed greater repeatable among-individual variation in behaviour. Additionally, individuals that were more familiar with each other exhibited lower within-individual variation in behaviour, providing one of the first examples of how the social environment can influence behavioural consistency. Our study demonstrates the potential for the social environment to generate and reinforce consistent individual differences in behaviour and provides a potentially general mechanism to explain this type of behavioural variation in animals with stable social groups.
Odours stimulate neuronal activity in the dorsolateral area of the hippocampal formation during path integration
Authors: Jorge P. E. , Phillips J. B. , Gonçalves A. , Marques P. A. M. , Nĕmec P.
Published: March 2014

The dorsolateral area of the hippocampal formation of birds is commonly assumed to play a central role in processing information needed for geographical positioning and homing. Previous work has interpreted odour-induced activity in this region as evidence for an ‘olfactory map’. Here, we show, using c-Fos expression as a marker, that neuronal activation in the dorsolateral area of the hippocampal formation of pigeons is primarily a response to odour novelty, not to the spatial distribution of odour sources that would be necessary for an olfactory map. Pigeons exposed to odours had significantly more neurons activated in this area of the brain than pigeons exposed to filtered air with odours removed. This increased activity was observed only in response to unfamiliar odours. No change in activity was observed when pigeons were exposed to home odours. These findings are consistent with non-home odours activating non-olfactory components of the pigeon's navigation system. The pattern of neuronal activation in the triangular and dorsomedial areas of the hippocampal formation was, by contrast, consistent with the possibility that odours play a role in providing spatial information.
Chloroplast DNA in Mature and Senescing Leaves: A Reappraisal
Authors: Golczyk Hieronim , Greiner Stephan , Wanner Gerhard , Weihe Andreas , Bock Ralph , Börner Thomas , Herrmann Reinhold G.
Published: March 2014

The fate of plastid DNA (ptDNA) during leaf development has become a matter of contention. Reports on little change in ptDNA copy number per cell contrast with claims of complete or nearly complete DNA loss already in mature leaves. We employed high-resolution fluorescence microscopy, transmission electron microscopy, semithin sectioning of leaf tissue, and real-time quantitative PCR to study structural and quantitative aspects of ptDNA during leaf development in four higher plant species (Arabidopsis thaliana, sugar beet [Beta vulgaris], tobacco [Nicotiana tabacum], and maize [Zea mays]) for which controversial findings have been reported. Our data demonstrate the retention of substantial amounts of ptDNA in mesophyll cells until leaf necrosis. In ageing and senescent leaves of Arabidopsis, tobacco, and maize, ptDNA amounts remain largely unchanged and nucleoids visible, in spite of marked structural changes during chloroplast-to-gerontoplast transition. This excludes the possibility that ptDNA degradation triggers senescence. In senescent sugar beet leaves, reduction of ptDNA per cell to ∼30% was observed reflecting primarily a decrease in plastid number per cell rather than a decline in DNA per organelle, as reported previously. Our findings are at variance with reports claiming loss of ptDNA at or after leaf maturation.
Fast Retrograde Signaling in Response to High Light Involves Metabolite Export, MITOGEN-ACTIVATED PROTEIN KINASE6, and AP2/ERF Transcription Factors in Arabidopsis
Authors: Vogel Marc Oliver , Moore Marten , König Katharina , Pecher Pascal , Alsharafa Khalid , Lee Justin , Dietz Karl-Josef
Published: March 2014

Regulation of the expression of nuclear genes encoding chloroplast proteins allows for metabolic adjustment in response to changing environmental conditions. This regulation is linked to retrograde signals that transmit information on the metabolic state of the chloroplast to the nucleus. Transcripts of several APETALA2/ETHYLENE RESPONSE FACTOR transcription factors (AP2/ERF-TFs) were found to respond within 10 min after transfer of low-light-acclimated Arabidopsis thaliana plants to high light. Initiation of this transcriptional response was completed within 1 min after transfer to high light. The fast responses of four AP2/ERF genes, ERF6, RRTF1, ERF104, and ERF105, were entirely deregulated in triose phosphate/phosphate translocator (tpt) mutants. Similarly, activation of MITOGEN-ACTIVATED PROTEIN KINASE6 (MPK6) was upregulated after 1 min in the wild type but not in the tpt mutant. Based on this, together with altered transcript regulation in mpk6 and erf6 mutants, a retrograde signal transmission model is proposed starting with metabolite export through the triose phosphate/phosphate translocator with subsequent MPK6 activation leading to initiation of AP2/ERF-TF gene expression and other downstream gene targets. The results show that operational retrograde signaling in response to high light involves a metabolite-linked pathway in addition to previously described redox and hormonal pathways.
Constructing an information science resource ontology based on the Chinese Social Science Citation Index
Authors: Qiu Junping , Lou Wen
Published: March 2014

Purpose

– The purpose of this study is to construct a Chinese information science resource ontology and to explore a new method for semiautomatic ontology construction.

Design/methodology/approach

– More than 8,290 articles indexed in the Chinese Social Science Citation Index (CSSCI), covering the years 2001 to 2010, were included in this study. Statistical analysis, co-occurrence analysis, and semantic similarity methods were applied to the selected articles. The ontology was built using existing construction principles and methods, as well as categories and hierarchy definitions based on CSSCI indexing fields.

Findings

– Seven categories were found to be relevant for the Chinese information science resource ontology, which, in this study, consists of a three-tier architecture, 78,291 instances, and 182,109 pairs of semantic relations. These results indicate the following: further improvements are required in ontology construction methods; resource ontology is a breakthrough concept in ontology studies; the combination of semantic similarities and co-occurrence analysis can quantitatively describe relationships between concepts.

Originality/value

– This study pioneers the resource ontology concept. It is one of the first to combine informetric methods with semantic similarity to reveal deep relationships in textual data.
Real estate ownership and closely-held firm value
Authors: Edward Graham John , Galbraith Craig , Stiles Curt
Published: March 2014

Purpose

– The authors aim to measure the value of leasing, versus owning, business locations for the closely-held firm.

Design/methodology/approach

– The authors examine the sales transactions of small businesses in the USA – those with revenues of less than $20 million per year – between 1995 and 2010. The authors contrast the values of firms that own, and do not own, their real estate.

Findings

– In general, the authors find negative relationships between closely-held firm values and real estate ownership. Nowhere did the authors observe firm value being enhanced by property ownership.

Research limitations/implications

– The data set may be limited by the accuracy of the data provided by business brokers. Compared to the capital markets, the small business “exchange” is less efficient, but it is the only source of unlisted business sales data.

Practical implications

– The findings are important to the small-business broker and the investor. The broker might better advise the buyer and seller with the findings. Business owners, private equity investors, and their advisors, are all reminded to focus on the core business strategy and avoid getting “locked into” real estate ownership in a business investment.

Originality/value

– The impact of real estate on the valuations of closely-held firms is a largely unexamined area. And there is a lack of consistency on publicly-held company valuations as a function of real estate ownership; these public company findings and the dearth of work on the privately-held company's real estate attract the attention in this study.
Psychic energy and synchronicity
Authors: Zabriskie Beverley
Published: March 2014

Given Jung's interest in physics’ formulations of psychic energy and the concept of time, overlaps and convergences in the themes addressed in analytical psychology and in quantum physics are to be expected. These are informed by the active intersections between the matter of mind and mindfulness re matter. In 1911, Jung initiated dinners with Einstein. Jung's definition of libido in the pivotal 1912 Fordham Lectures reveals the influence of these conversations. Twenty years later, a significant period in physics, Wolfgang Pauli contacted Jung. Their collaboration led to the theory of synchronicity.
Collecting and Analyzing DNA Evidence from Fingernails: A Comparative Study,,
Authors: Hebda Lisa M. , Doran Ashley E. , Foran David R.
Published: March 2014

Forensic practitioners and crime laboratories regularly collect and analyze fingernail evidence; however, the best techniques for processing such evidence have not been established. In this study, numerous aspects of fingernail evidence processing—collection of exogenous cells, transportation, purification of DNA, and STR analysis—were analyzed using fingernails harboring applied blood or epithelial cells from scratchings. Autosomal STR mixtures resulted when fingernails were soaked or swabbed, while scrapings rarely generated mixtures but exhibited allelic dropout. Y‐STRs yielded single source profiles, with scrapings again showing dropout. A silica‐based kit extraction recovered significantly more exogenous DNA than did organic extraction, neither of which was affected by nail polish. Swabbing nails in succession resulted in some cross‐contamination from exogenous material, while transporting nails together did not, although there was loss of exogenous cells. Optimized nail processing produced complete Y‐STR profiles of male volunteers from female fingernails following scratchings.
Relationship Between Residual Renal Function and Serum Fibroblast Growth Factor 23 in Patients on Peritoneal Dialysis
Authors: Yamada Shunsuke , Tsuruya Kazuhiko , Taniguchi Masatomo , Yoshida Hisako , Tokumoto Masanori , Hasegawa Shoko , Tanaka Shigeru , Eriguchi Masahiro , Nakano Toshiaki , Kitazono Takanari
Published: March 2014

Fibroblast growth factor 23 (FGF23) levels in dialysis patients are influenced by various factors, including phosphorus load. However, the clinical parameters that determine serum FGF23 levels in patients on peritoneal dialysis (PD) remain unclear. The aim of the present study was to examine the effects of clinical factors, on serum FGF23 levels, with an emphasis on residual renal function (RRF). This cross‐sectional study included 56 outpatients undergoing PD therapy. Urine volume ≥100 mL/day or renal creatinine (Cr) clearance was used as a surrogate marker for RRF. Clinical characteristics were compared between patients with and without RRF. Linear regression analysis was conducted with serum FGF23 level as the dependent variable and renal Cr clearance as the main independent variable. The median and interquartile range of serum FGF23 levels were 5970 (1451–11 688) pg/mL. Patients with RRF showed higher urinary and total phosphate eliminations, and lower serum FGF23 and phosphate levels than patients without RRF. Multivariate linear regression analysis showed that the renal Cr clearance and serum phosphate and dialysis history were negatively associated with serum FGF23 levels, even after adjusting for potential confounders including peritoneal Cr clearance. Further, the predictabilities of serum FGF23 were comparable among renal Cr clearance, Kt/V for urea, and renal phosphate clearance. RRF determined by renal Cr clearance or residual urine volume is an independent negative determinant of serum FGF23 levels in PD patients.
The flexible coefficient multinomial logit (FC‐MNL) model of demand for differentiated products
Authors: Davis Peter , Schiraldi Pasquale
Published: March 2014

We show FC‐MNL is flexible in the sense of Diewert (), thus its parameters can be chosen to match a well‐defined class of possible own‐ and cross‐price elasticities of demand. In contrast to models such as Probit and Random Coefficient‐MNL models, FC‐MNL does not require estimation via simulation; it is fully analytic. Under well‐defined and testable parameter restrictions, FC‐MNL is shown to be an unexplored member of McFadden's class of Multivariate Extreme Value discrete‐choice models. Therefore, FC‐MNL is fully consistent with an underlying structural model of heterogeneous, utility‐maximizing consumers. We provide a Monte‐Carlo study to establish its properties and we illustrate its use by estimating the demand for new automobiles in Italy.
The welfare effects of third‐degree price discrimination in intermediate good markets: the case of bargaining
Authors: O'Brien Daniel P.
Published: March 2014

This article examines the welfare effects of third‐degree price discrimination by a monopolist selling to downstream firms with bargaining power. One of the downstream firms (the “chain store”) can integrate backward at lower cost than rivals. Bargaining powers also depend on disagreement profits, bargaining weights, and concession costs. If the chain's integration threat is not credible, price discrimination reduces the input price charged symmetric downstream firms and often reduces the average input price charged asymmetric downstream firms.
Communication and authority with a partially informed expert
Authors: Agastya Murali , Bag Parimal Kanti , Chakraborty Indranil
Published: March 2014

A sender‐receiver game a la Crawford‐Sobel is analyzed where the sender has expertise on some but not all the payoff‐relevant factors. This residual uncertainty can either improve (even allow full revelation) or worsen the quality of transmitted information depending on a statistic called the effective bias. For symmetrically distributed residual uncertainty or quadratic loss functions, (i) the quality of information transmission is independent of the riskiness of residual uncertainty, (ii) it may be suboptimal to allocate authority to the informed player, (iii) despite players' preferences being arbitrarily close, it is impossible to assert that the receiver prefers delegation over authority or vice versa.
GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids
Authors: Izuhara Y. , Matsumoto H. , Kanemitsu Y. , Izuhara K. , Tohda Y. , Horiguchi T. , Kita H. , Kuwabara K. , Tomii K. , Otsuka K. , Fujimura M. , Ohkura N. , Tomita K. , Yokoyama A. , Ohnishi H. , Nakano Y. , Oguma T. , Hozawa S. , Nagasaki T. , Ito I. , Oguma T. , Inoue H. , Tajiri T. , Iwata T. , Ono J. , Ohta S. , Tamari M. , Hirota T. , Yokoyama T. , Niimi A. , Mishima M.
Published: March 2014

Background

In steroid‐naive patients with asthma, several gene variants are associated with a short‐term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1) and the variant of the glucocorticoid‐induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long‐term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation.

Methods

In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single‐nucleotide polymorphisms (SNPs) in GLCCI1, stress‐induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined.

Results

Besides the known contributing factors, that is, the most intensive treatment step, ex‐smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group.

Conclusions

A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long‐term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
A reproducible automated segmentation algorithm for corneal epithelium cell images from in vivo laser scanning confocal microscopy
Authors: Bullet Julien , Gaujoux Thomas , Borderie Vincent , Bloch Isabelle , Laroche Laurent
Published: March 2014

Purpose

To evaluate an automated process to find borders of corneal basal epithelial cells in pictures obtained from in vivo laser scanning confocal microscopy (Heidelberg Retina Tomograph III with Rostock corneal module).

Methods

On a sample of 20 normal corneal epithelial pictures, images were segmented through an automated four‐step segmentation algorithm. Steps of the algorithm included noise reduction through a fast Fourier transform (FFT) band‐pass filter, image binarization with a mean value threshold, watershed segmentation algorithm on distance map to separate fused cells and Voronoi diagram segmentation algorithm (which gives a final mask of cell borders). Cells were then automatically counted using this border mask. On the original image either with contrast enhancement or noise reduction, cells were manually counted by a trained operator.

Results

The average cell density was 7722.5 cells/mm2 as assessed by automated analysis and 7732.5 cells/mm2 as assessed by manual analysis (p = 0.93). Correlation between automated and manual analysis was strong (r = 0.974 [0.934–0.990], p < 0.001). Bland–Altman method gives a mean difference in density of 10 cells/mm2 and a limits of agreement ranging from −971 to +991 cells/mm2. Visually, the algorithm correctly found almost all borders.

Conclusion

This automated segmentation algorithm is worth for assessing corneal epithelial basal cell density and morphometry. This procedure is fully reproducible, with no operator‐induced variability.
Role of non‐coding RNAs in pancreatic beta‐cell development and physiology
Authors: Eliasson L. , Esguerra J. L. S.
Published: March 2014

The progression of diabetes is accompanied by increasing demand to the beta‐cells to produce and secrete more insulin, requiring complex beta‐cell adaptations. Functionally active and ubiquitous non‐coding RNAs (ncRNAs) have the capacity to take part in such adaptations as they have been shown to be key regulatory molecules in various biological processes. In the pancreatic islets, the function of ncRNAs and their contribution to disease development is beginning to be understood. Here, we review the different classes of ncRNAs, such as long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs), and their potential contribution to insulin secretion. A special focus will be on miRNAs and their regulatory function in beta‐cell physiology and insulin exocytosis. As important players in gene regulation, ncRNAs have huge potential in opening innovative therapeutic avenues against diabetes and associated complications.
Modular organization of cardiac energy metabolism: energy conversion, transfer and feedback regulation
Authors: Guzun R. , Kaambre T. , Bagur R. , Grichine A. , Usson Y. , Varikmaa M. , Anmann T. , Tepp K. , Timohhina N. , Shevchuk I. , Chekulayev V. , Boucher F. , Dos Santos P. , Schlattner U. , Wallimann T. , Kuznetsov A. V. , Dzeja P. , Aliev M. , Saks V.
Published: March 2014

To meet high cellular demands, the energy metabolism of cardiac muscles is organized by precise and coordinated functioning of intracellular energetic units (ICEUs). ICEUs represent structural and functional modules integrating multiple fluxes at sites of ATP generation in mitochondria and ATP utilization by myofibrillar, sarcoplasmic reticulum and sarcolemma ion‐pump ATPases. The role of ICEUs is to enhance the efficiency of vectorial intracellular energy transfer and fine tuning of oxidative ATP synthesis maintaining stable metabolite levels to adjust to intracellular energy needs through the dynamic system of compartmentalized phosphoryl transfer networks. One of the key elements in regulation of energy flux distribution and feedback communication is the selective permeability of mitochondrial outer membrane (MOM) which represents a bottleneck in adenine nucleotide and other energy metabolite transfer and microcompartmentalization. Based on the experimental and theoretical (mathematical modelling) arguments, we describe regulation of mitochondrial ATP synthesis within ICEUs allowing heart workload to be linearly correlated with oxygen consumption ensuring conditions of metabolic stability, signal communication and synchronization. Particular attention was paid to the structure–function relationship in the development of ICEU, and the role of mitochondria interaction with cytoskeletal proteins, like tubulin, in the regulation of MOM permeability in response to energy metabolic signals providing regulation of mitochondrial respiration. Emphasis was given to the importance of creatine metabolism for the cardiac energy homoeostasis.
Changes in the activity and expression of protein phosphatase‐1 accompany the differential regulation of NHE3 before and after the onset of hypertension in spontaneously hypertensive rats
Authors: Crajoinas R. O. , Pessoa T. D. , Rodrigues M. V. , Malnic G. , Girardi A. C. C.
Published: March 2014

Aim

The Na+/H+ exchanger NHE3 activity decreases in the proximal tubule of spontaneously hypertensive rats (SHRs) as blood pressure increases, and this reduction is correlated with higher NHE3 phosphorylation levels at the PKA consensus site serine 552. This study tested the hypothesis that this lowered NHE3 activity is associated with an increase in PKA activity and expression, and/or a decrease in protein phosphatase‐1 (PP1) activity and expression.

Methods

Proximal tubule NHE3 activity was measured as the rate of bicarbonate reabsorption by stationary microperfusion. NHE3 phosphorylation and protein expression were determined by immunoblotting. PKA and PP1 activities were determined using specific substrates under optimal enzymatic conditions.

Results

The PKA activator, 6‐MB‐cAMP, increased the phosphorylation levels of NHE3 at serine 552 in the renal cortex; this increase happens to a much greater extent in young pre‐hypertensive SHRs (Y‐SHRs) compared to adult SHRs with established hypertension (A‐SHRs). Likewise, the inhibitory effect of 6‐MB‐cAMP on NHE3 transport activity was much more pronounced in the proximal tubules of Y‐SHRs than in those of A‐SHRs. Renal cortical activity of PKA was not significantly different between Y‐SHRs and A‐SHRs. On the other hand, Y‐SHRs exhibited higher protein phosphatase 1 (PP1) activity, and their expression of the PP1 catalytic subunit PP1α in the renal cortex was also higher than in A‐SHRs.

Conclusion

Collectively, these results support the idea that the lower NHE3 transport activity and higher phosphorylation occurring after the development of hypertension in SHRs are due, at least in part, to reduced PP1‐mediated dephosphorylation of NHE3 at serine 552.
Anti‐viral therapy for prevention of perinatalHBVtransmission: extending therapy beyond birth does not protect against post‐partum flare
Authors: Nguyen V. , Tan P. K. , Greenup A.‐J. , Glass A. , Davison S. , Samarasinghe D. , Holdaway S. , Strasser S. I. , Chatterjee U. , Jackson K. , Locarnini S. A. , Levy M. T.
Published: March 2014

Background

Antepartum anti‐viral therapy (AVT) is often administered to prevent perinatal transmission of hepatitis B virus (HBV) infection. Little is known about the effect ofAVTon post‐partum flare rates and severity.

Aim

To examine whether extendingAVTbeyond birth influences the post‐partum course.

Methods

One hundred and one pregnancies in 91 women with HBV DNA levels ≥log 7 IU/mLwere included. AVT (initially lamivudine, later tenofovir disoproxil fumarate) was commenced from 32 weeks gestation and stopped soon after birth and at 12 weeks post‐partum. Outcomes according to post‐partum treatment duration were examined: Group 1 = AVT ≤4 weeks (n = 44), Group 2 = AVT >4 weeks (n = 43), Group 3 = no AVT (n = 14).

Results

The majority of women were HBeAg+ (97%), median age 29 years, baseline HBV DNA log 8.0 IU/mLand follow‐up 48 weeks post‐partum. Post‐partum treatment duration was 2 weeks for Group 1 and 12 weeks for Group 2,P < 0.01. Flare rates were not significantly different: Group 1 = 22/44 (50%), Group 2 = 17/43 (40%) and Group 3 = 4/14 (29%),P = 0.32. Onset of flare was similar at 8/10/9 weeks post‐partum for Groups 1/2/3 respectively,P = 0.34. The majority of flares spontaneously resolved. HBeAg seroconversion (n = 1/5/1 in Groups 1/2/3,P = 0.27) was not associated with treatment duration or the occurrence of a post‐partum flare.

Conclusions

Post‐partum flares are common and usually arise early after delivery. They are often mild in severity and most spontaneously resolve. Extending anti‐viral therapy does not protect against post‐partum flares or affectHBeAg seroconversion rates.
Sustainable city‐building and the new politics of the possible: reflections on the governance of the London Olympics 2012
Authors: Raco Mike
Published: March 2014

This paper draws on the example of the London Olympics 2012 to argue that a new ‘realistic’ politics of good governance and output‐focused private sector delivery now dominates sustainability policy thinking. It is a politics that makes a series of normative claims and promises based on a pragmatic and non‐ideological approach to sustainability. Its advocates claim that it converts the lofty ideals and aspirations of utopian sustainability into tangible, verifiable and output‐based delivery mechanisms. The discussion examines the governance arrangements that were put in place for the Games and the ways in which sustainability objectives were defined, institutionalised and mobilised by hybrid public and private actors. It outlines some of the wider impacts of this new development model and its implications for thinking about sustainability planning elsewhere.
Instrument breakage as a complication of elbow arthroscopy in a dog
Authors: Grand JG , Roig JA , de Swarte M
Published: March 2014

Case report

We describe an unusual complication of a routine arthroscopic procedure to treat fragmentation of the medial portion of the coronoid process in a 1‐year‐oldLabradorRetriever. While the lesion was being curetted, the tip of the arthroscopic curette broke off. Attempts were made to remove it, but failed, and the broken fragment migrated out of the arthroscopic field. Conversion from arthroscopy to arthrotomy was unsuccessful. On intraoperative radiographs, the metallic fragment was detected in the radial fossa of the humeral condyle. A limited surgical approach to this area, guided by ultrasound, also proved ineffective. Finally, the broken curette tip was left in situ. The dog made an uneventful recovery and 6 months after surgery it showed no lameness except after rest and there was no evidence of migration of the metallic fragment on radiographs.

Conclusions

On such occasions, we recommend: (1) stop both the inflow and outflow of fluids; (2) attempt arthroscopic retrieval with a magnetic retriever and large forceps; (3) use diagnostic imaging to localise the broken fragment if it migrates out of the arthroscopic field; and (4) leave in situ if it is no longer accessible to arthroscopic extraction. This is the first report of an instrument breakage during arthroscopy in a dog.
Can Physical Exercise or Food Deprivation Cause Release of Fat‐Stored Cannabinoids?
Authors: Westin Andreas Austgulen , Mjønes George , Burchardt Ola , Fuskevåg Ole Martin , Slørdal Lars
Published: March 2014

The aim of this study was to evaluate whether physical exercise or food deprivation may increase cannabinoid levels in serum or urine in abstinent chronic cannabis users. The study took place in a drug detoxification ward parallel to study participants receiving treatment. Six chronic, daily cannabis users (one female, five males, average age 30.0 years; BMI 20.8) were exposed to a 45‐min. moderate‐intensity workout and a 24‐hr period of food deprivation. Serum samples were drawn prior to and after interventions and analysed for ∆9‐tetrahydrocannabinol (THC) and 11‐nor‐9‐carboxy‐∆9‐tetrahydrocannabinol (THCCOOH) by liquid chromatography–tandem mass spectrometry (LCMSMS), and all voided urine was tested for THCCOOH by LCMSMS and normalized to the creatinine levels, yielding ng/mg ratios. There were no major differences in the measured cannabinoid levels in serum or urine before and after physical exercise or food deprivation. We conclude that exercise and/or food deprivation are unlikely to cause sufficient cannabinoid concentration changes to hamper correct interpretations in drug testing programmes.
Impaired proplatelet formation in immune thrombocytopenia: a novel mechanism contributing to decreased platelet count
Authors: Lev Paola R. , Grodzielski Matías , Goette Nora P. , Glembotsky Ana C. , Espasandin Yesica R. , Pierdominici Marta S. , Contrufo Geraldine , Montero Verónica S. , Ferrari Luciana , Molinas Felisa C. , Heller Paula G. , Marta Rosana F.
Published: March 2014

The pathophysiological mechanisms contributing to the decreased platelet count in immune thrombocytopenia (ITP) are not entirely understood. Here, we investigated the key step of proplatelet formation (PPF) by studying the effect of ITP plasma in thrombopoiesis. Normal cord blood‐derived mature megakaryocytes were cultured in the presence of recalcified plasma from ITP patients, and PPF was evaluated by microscopic analysis. Patient samples induced a dose‐dependent inhibition in PPF, as well as decreased complexity of proplatelet architecture. Although slightly increased, plasma‐induced megakaryocyte apoptosis was not related to PPF impairment. Purified IgG reproduced the inhibitory effect, while platelet‐adsorbed plasma induced its reversion, suggesting the involvement of auto‐antibodies in the inhibition of thrombopoiesis. Impaired PPF, induced by ITP plasmas bearing anti‐GPIIb‐IIIa antibodies, was related to their ability to interfere with the normal function of this integrin, as assessed by megakaryocyte PAC‐1 binding and β3 integrin phosphorylation while the presence of anti‐glycoprotein Ia‐IIa auto‐antibodies was associated with loss of normal inhibition of PPF induced by type I collagen. In conclusion, abnormal thrombopoiesis comprising decreased PPF and morphological changes in proplatelet structure are induced by patient samples, unveiling new mechanisms contributing to decreased platelet count in ITP.
Osteonecrosis of the jaw and renal safety in patients with newly diagnosed multiple myeloma: Medical Research Council Myeloma IX Study results
Authors: Jackson Graham H. , Morgan Gareth J. , Davies Faith E. , Wu Ping , Gregory Walter M. , Bell Sue E. , Szubert Alexander J. , Navarro Coy Nuria , Drayson Mark T. , Owen Roger G. , Feyler Sylvia , Ashcroft Andrew J. , Ross Fiona M. , Byrne Jennifer , Roddie Huw , Rudin Claudius , Boyd Kevin D. , Osborne Wendy L. , Cook Gordon , Child J. Anthony
Published: March 2014

Bisphosphonates are recommended in patients with osteolytic lesions secondary to multiple myeloma. We report on the safety of bisphosphonate therapy with long‐term follow‐up in the Medical Research Council Myeloma IX study. Patients with newly diagnosed multiple myeloma were randomised to zoledronic acid (ZOL; 4 mg intravenously every 21–28 d) or clodronate (CLO; 1600 mg/d orally) plus chemotherapy. Among 1960 patients (5·9‐year median follow‐up), both bisphosphonates were well tolerated. Acute renal failure events were similar between groups (ZOL 5·2% vs. CLO 5·8% at 2 years; incidence plateaued thereafter). The overall incidence of confirmed osteonecrosis of the jaw (ONJ) was low, but higher with ZOL (ZOL 3·7% vs. CLO 0·5%; P < 0·0001). ONJ events were generally low grade and most occurred between 8 and 30 months (median time to ONJ, 23·7 months). Among 10 patients with ONJ recovery data, four patients in the ZOL group completely recovered, two patients improved, and three patients experienced no improvement; one CLO patient experienced no improvement. Dental surgery or trauma preceded ONJ in six ZOL patients. The incidence of renal adverse events was similar for ZOL and CLO. ONJ incidence remained low and was lower with CLO compared to ZOL. We have seen no further ONJ cases to date.
Neuropathological Staging of Spinocerebellar Ataxia Type 2 by Semiquantitative 1C2‐Positive Neuron Typing. Nuclear Translocation of Cytoplasmic 1C2 Underlies Disease Progression of Spinocerebellar Ataxia Type 2
Authors: Koyano Shigeru , Yagishita Saburo , Kuroiwa Yoshiyuki , Tanaka Fumiaki , Uchihara Toshiki
Published: March 2014

Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by the expansion of the trinucleotide CAG repeats encoding elongated polyglutamine tract in ataxin‐2, the SCA2 gene product. Polyglutamine diseases comprise nine genetic entities, including seven different forms of spinocerebellar ataxias, Huntington's disease, and spinal and bulbar muscular atrophy. These are pathologically characterized by neuronal loss and intranuclear aggregates or inclusions of mutant proteins including expanded polyglutamine in selected neuronal groups. Previously, we examined immunolocalization of ubiquitin, expanded polyglutamine (probed by 1C2 antibody), and ataxin‐2 in genetically confirmed SCA2 patients. In the present study, we expanded this approach by distinguishing different patterns of subcellular 1C2 immunoreactivity (“granular cytoplasmic,” “cytoplasmic and nuclear” and “nuclear with inclusions.”) and by quantifying their regional frequencies in three autopsied SCA2 brains at different stage of the disease. Comparison with neuronal loss and gliosis revealed that overall 1C2 immunoreactivity was paralleled with their severity. Furthermore, appearance of granular cytoplasmic pattern corresponded to early stage, cytoplasmic and nuclear pattern to active stage, and nuclear with inclusions pattern to final stage. We conclude that this 1C2‐immunoreactive typing may be useful for evaluating the overall severity and extent of affected regions and estimating the neuropathological stage of SCA2.
LIM protein JUB promotes epithelial–mesenchymal transition in colorectal cancer
Authors: Liang Xing‐Hua , Zhang Guang‐Xian , Zeng Yue‐bin , Yang Hai‐Feng , Li Wen‐Hong , Liu Qi‐Long , Tang Yue‐liang , He Wen‐guang , Huang Yan‐Nian , Zhang Lei , Yu Li‐Na , Zeng Xian‐Cheng
Published: March 2014

Metastasis is the leading cause of cancer‐related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial–mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain‐containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail‐induced EMT. The expression of JUB shows an inverse correlation with E‐cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor‐promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.
Serum carotenoid levels and risk of lung cancer death in US adults
Authors: Min Kyoung‐bok , Min Jin‐young
Published: March 2014

Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer‐induced death in the USA. Although much attention has been focused on the anti‐carcinogenic effect of consuming carotenoid‐containing food or supplements, the results have been inconsistent. We investigated whether serum carotenoid levels were associated with the mortality risk of lung cancer in US adults using data from a nationally representative sample. The data were obtained from the Third Nutrition and Health Examination Survey (NHANES III) database and the NHANES III Linked Mortality File. A total of 10 382 participants aged over 20 years with available serum carotenoid levels and no other missing information on questionnaires and biomarkers at baseline (NHANES III) were included in the present study. Of the 10 382 participants, 161 subjects died due to lung cancer. We found that high serum levels of alpha‐carotene and beta‐cryptoxanthin at baseline were significantly associated with a lower risk of lung cancer death. When we stratified the risk by current smoking status, the risk of death of current smokers was significantly decreased to 46% (95% confidence interval, 31–94%) for alpha‐carotene and 61% (95% confidence interval, 19–80%) for beta‐cryptoxanthin. By contrast, no association was observed among never/former smokers at baseline. High serum levels of alpha‐carotene and beta‐cryptoxanthin are associated with a lower risk of lung cancer death in US adults.
Synthesis and Anti‐HIV Activity of 4‐(Naphthalen‐1‐yl)‐1,2,5‐thiadiazol‐3‐hydroxyl Derivatives
Authors: Rai Diwakar , Chen Wenmin , Zhan Peng , Liu Hong , Tian Ye , Liang Xin , De Clercq Erik , Pannecouque Christophe , Balzarini Jan , Liu Xinyong
Published: March 2014

A series of 4‐(naphthalen‐1‐yl)‐1,2,5‐thiadiazol‐3‐hydroxyl derivatives (Ia–Im and IIa–IIe) designed as novel HIV‐1 non‐nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized via an expeditious route and evaluated for their anti‐HIV activities in MT‐4 cell cultures. All the synthesized compounds were structurally confirmed by spectral analyses. Biological results showed that three analogues displayed moderate inhibitory activity against wild‐type (wt) HIV‐1 replication with EC50 values ranging from 16 to 22 μm. Molecular docking of compound Ih with wt HIV‐1 RT was performed to understand the binding mode between these inhibitors and the wt HIV‐1 RT and to rationalize some SARs.
Microglial modulation as a mechanism behind the promotion of central nervous system well‐being by physical exercise
Authors: Jensen Samuel K. , Yong V. Wee
Published: March 2014

The role of microglia within the central nervous system (CNS), and their contribution to processes critical for both normal function and the development of pathology have expanded significantly in recent years. Distinct microglial subpopulations are described that exert differential effects depending on region, environmental cues and activation state. This has led to the proposition of microglia as a novel therapeutic target in a variety of CNS disorders. Exercise has recently been shown to reduce the chronic activation and aberrant regulation of microglia that occurs during pathology, and to promote the adoption of neuroprotective phenotypes. This is thought to translate into decreased destruction of dopaminergic neurons in models of Parkinson's disease, the promotion of hippocampal neurogenesis, and the reduction of age‐induced neuroinflammation and microglial priming. The present review will detail the emerging evidence suggesting microglial modulation as a key mechanism through which exercise exerts beneficial effects on the CNS. Here, we will present the role of microglia within select CNS processes/disorders, and describe how physical exercise improves CNS well‐being by directly acting through microglia. Finally, we discuss considerations of implementation of exercise as a therapeutic intervention in neurological disorders.