bluuebunny/crossref_metadata_2025 huggingface dataset:
DADS neuropathy associated with anti-TNF-α therapy
Authors: McGinty Ronan Niall , McNamara Brian , Moore Helena
Published: November 2015

A 52-year-old man with idiopathic Parkinson's disease and severe rheumatoid arthritis presented with a 1-year history of progressively worsening limb paraesthesia. Examination showed sensory loss in a glove and stocking distribution, absent reflexes and unsteady tandem gait. Nerve conduction studies suggested an acquired peripheral neuropathy with distal demyelination, which—together with the clinical phenotype—was consistent with a Distal Acquired Demyelinating Symmetric (DADS) neuropathy pattern. This was attributed to therapy with adalimumab, an antitumor necrosis factor (TNF)-α agent, which the patient had been taking for 2 years for rheumatoid arthritis. One month after discontinuing adalimumab, the limb paraesthesia had resolved completely and the patient had a normal tandem gait. Demyelinating disorders may rarely occur as complications of anti-TNF-α agents and therefore have implications for pretreatment counselling and ongoing monitoring. DADS neuropathy is a subtype of chronic inflammatory demyelinating polyradiculoneuropathy, which responds poorly to standard therapy and has not previously been described with anti-TNF-α therapy.
Bilateral total hip replacement in arthrogryposis multiplex congenita
Authors: Dalton David Michael , Magill Paul , Mulhall Kevin James
Published: November 2015

The authors present a case of bilateral total hip replacements (THRs) in a 56-year-old patient with arthrogryposis multiplex congenita (AMC). The considerations for the perioperative period and the outcome are discussed. Preoperative planning included an anaesthetic review and availability of fiberoptic intubation due to poor mouth opening. Perioperatively, contractures can make positioning and exposure difficult but in this case a standard posterior approach was taken. Particular attention was given to soft tissue balancing given the theoretical risk of dislocation. There were no perioperative complications. Postoperatively there has been improvement in pain and hip scores but the patient has failed to return to work. Objective improvements in range of motion (ROM) have not been made. This experience suggests THR is a safe and effective treatment for osteoarthritic hip pain in patients with AMC but patients should be informed that ROM is unlikely to improve.
Comparison of birth weight between school health records and medical birth records in Denmark: determinants of discrepancies
Authors: Jensen Camilla Bjørn , Gamborg Michael , Heitmann Berit , Sørensen Thorkild I A , Baker Jennifer L
Published: November 2015

Objective

To compare reported birth weight (BW) information in school health records with BW from medical birth records, and to investigate if maternal and offspring characteristics were associated with any discrepancies.

Design

Register-based cohort study.

Setting

Denmark, 1973–1991.

Participants

The study was based on BW recorded in the Copenhagen School Health Records Register (CSHRR) and in The Medical Birth Register (MBR). The registers were linked via the Danish personal identification number.

Primary and secondary outcome measures

Statistical comparisons of BW in the registers were performed using t tests, Pearson's correlation coefficients, Bland-Altman plots and κ coefficients. Odds of BW discrepancies >100 g were examined by logistic regressions.

Results

The study population included 47 534 children. From 1973 to 1979 when BW was grouped in 500 g intervals in the MBR, mean BW differed significantly between the registers. During 1979–1991 when BW was recorded in 10 and 1 g intervals, mean BW did not significantly differ between the two registers. BW from both registers was highly correlated (0.93–0.97). Odds of a BW discrepancy significantly increased with parity, the child's age at recall and by marital status (children of married women had the highest odds).

Conclusions

Overall, BW information in school health records agreed very well with BW from medical birth records, suggesting that reports of BWs in school health records in Copenhagen, Denmark generally are valid.
Use of high doses of folic acid supplements in pregnant women in Spain: an INMA cohort study
Authors: Navarrete-Muñoz Eva María , Valera-Gran Desirée , García de la Hera Manoli , Gimenez-Monzo Daniel , Morales Eva , Julvez Jordi , Riaño Isolina , Tardón Adonina , Ibarluzea Jesus , Santa-Marina Loreto , Murcia Mario , Rebagliato Marisa , Vioque Jesus
Published: November 2015

Objectives

We examined the use of low (<400 μg/day, including no use) and high folic acid supplement (FAS) dosages (≥1000 μg/day) among pregnant women in Spain, and explored factors associated with the use of these non-recommended dosages.

Design

Population-based cohort study.

Setting

Spain.

Participants

We analysed data from 2332 pregnant women of the INMA study, a prospective mother-child cohort study in Spain.

Main outcome measures

We assessed usual dietary folate and the use of FAS from preconception to the 3rd month (first period) and from the 4th to the 7th month (second period), using a validated food frequency questionnaire. We used multinomial logistic regression to estimate relative risk ratios (RRRs).

Results

Over a half of the women used low dosages of FAS in the first and second period while 29% and 17% took high dosages of FAS, respectively. In the first period, tobacco smoking (RRR=1.63), alcohol intake (RRR=1.40), multiparous (RRR=1.44), unplanned pregnancy (RRR=4.20) and previous spontaneous abortion (RRR=0.58, lower use of high FAS dosages among those with previous abortions) were significantly associated with low FAS dosages. Alcohol consumption (RRR=1.42), unplanned pregnancy (RRR=2.66) and previous spontaneous abortion (RRR=0.68) were associated with high dosage use. In the second period, only tobacco smoking was significantly associated with high FAS dosage use (RRR=0.67).

Conclusions

A high proportion of pregnant women did not reach the recommended dosages of FAS in periconception and a considerable proportion also used FAS dosages ≥1000 μg/day. Action should be planned by the Health Care System and health professionals to improve the appropriate periconceptional use of FAS, taking into consideration the associated factors.
Republished: Basic science behind the cardiovascular benefits of exercise
Authors: Wilson Mathew G , Ellison Georgina M , Cable N Tim
Published: November 2015

Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5–20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be.
Biogeography of island floras in the Great Lakes. I. Species richness and composition in relation to gull nesting activities
Authors: Hogg E. H. , Morton J. K. , Venn Joan M.
Published: November 2015

Species–area relations of vascular plants and the effect of nesting colonies of gulls on plant species composition were investigated for 77 islands in Georgian Bay and Lake Huron in the Great Lakes region of Canada. The percentage of plant species classed as alien, annual, or biennial was significantly greater on islands with gull colonies. The slope of the species–area curve was significantly steeper on islands supporting gull colonies compared with islands lacking gull colonies. The expected decline in species richness with increased island remoteness was not detected statistically using multiple regression analysis. The difference in species–area slopes does not appear to reflect a lower propagule immigration rate to islands with gull colonies, because gulls are important in the dispersal of alien plant species to these islands. Larger islands with gull colonies tended to have richer floras than islands of similar size without gull colonies. It is suggested that on these larger islands the presence of gull colonies produces a gradient of soil nutrient and disturbance regimes, thus increasing habitat heterogeneity and species richness.
Genomic variability in the vascular cambium of Abies balsamea
Authors: Mellerowicz E. J. , Riding R. T. , Little C. H. A.
Published: November 2015

DNA content was measured cytophotometrically in Feulgen-stained nuclei of fusiform cambial initials from 1- (twig) and 19-year-old (stem base) cambia of balsam fir (Abies balsamea) trees throughout the season. Telophase (2C) and prophase (4C) DNA contents varied with both cambial age and time of year. Maximum DNA contents were observed at the beginning of cambial activity in April. They were lower in the 1-year-old cambium (42.3 (2C) and 84.3 (4C) pg DNA) than in the 19-year-old cambium (59.4 (2C) and 111.1 (4C) pg DNA). The DNA levels decreased during the cambial growing season, attaining minimal values in September of 28.3 (2C) and 53.5 (4C) pg and 37.9 (2C) and 74.5 (4C) pg in the 1- and 19-year-old cambia, respectively. In the autumn, cells accumulated in the G1 phase of the cell cycle. DNA synthesis then took place increasing the 2C levels from the minimum values to the maximum values. This DNA synthesis in 1-year-old cambia started before the beginning of the transition from the resting to the quiescent stage of dormancy.
Release of esterase from wounded potato tubers and evidence for its presence on the plasma membrane
Authors: Davis David A. , Currier William W. , Racusen David
Published: November 2015

Esterase activity, obtained from the surface of tuber slices, increases significantly when the slices are treated with water and aged in air. This rise in esterase activity was prevented if the tuber surface was treated with unsaturated fatty acids which are toxic to tuber cells. The fatty acids did not inhibit the activity of purified esterase. Also, application of inhibitors of active oxygen to the tuber surface did not prevent the reduction of esterase obtained following fatty acid treatments. It is suggested that fatty acids inhibit the release of esterase from the cells. This is supported by the detection of patatin (the glycoprotein responsible for the esterase activity) on the cell membrane as judged by the agglutination of isolated protoplasts with low levels of patatin antiserum.
Chrysanthemum phloem necrosis: symptomatology and histopathology
Authors: McGovern R. J. , Horst R. K. , Israel H. W.
Published: November 2015

The symptomatology and histopathology of chrysanthemum phloem necrosis, a new disease of florists' chrysanthemum was investigated. The disease results in flecking, yellowing, and premature deterioration of lower leaves and flower distortion in the Dendranthema grandiflora Tzveler. (syns. D. morifolia Ramat., Chrysanthemum morifolium Ramat.) Marble cultivar group. Cleared leaves of 'Pink Marble' revealed vascular browning in midveins and secondary veins that was enhanced at 32 °C. The sieve elements and associated cells in affected leaves were often necrotic and collapsed, a condition that was aggravated by elevated temperature. Spherical-to-elongate mycoplasmalike organisms, 0.2–1.0 μm diameter, were observed only in infected plants within collapsed sieve elements. Mycoplasmalike organisms were not detected in uninfected plants; sieve-plate elements contained merely fibrillar p-protein, a normal cell component. In comparison to uninfected plants abnormal callose accumulation and lignin formation were observed in the phloem of infected plants, and elevated levels of phenolic materials were found in vascular and nonvascular tissues.
Conditions d'apparition d'une embryogénèse somatique sur des cals issus de la culture de tissus foliaires du chêne vert (Quercus ilex)
Authors: Féraud-Keller C. , Espagnac H.
Published: November 2015

The proliferation of parenchymatous foliar tissue of Quercus ilex was obtained from current year leaves taken from old trees and cultivated in vitro on modified Murashige and Skoog's medium supplemented with benzylaminopurine (4 mg ∙ L−1) and naphthyl acetic acid (0.5 mg ∙ L−1). Only the fragments cultured in October reacted. The neoformations only appeared on calluses that had not been subcultured for 7 months. Primary nodules arising on these calluses were removed and subcultured on the same medium either in the dark or in the light. In the dark only, they produced secondary nodules, which were the source of somatic embryos both in light and dark. Presently, they seem to regulate their structure in the dark but they do not develop in a way that leads to germination.
The influence of Rhizobium trifolii on growth characteristics of Trifolium repens: integration of local environments by clonal genets of T. repens
Authors: Shivji Amin , Turkington Roy
Published: November 2015

Seven replicate clones of Trifolium repens were each grown such that the two halves of each clone were growing in different environments, one half in sterilized soil with an added inoculum of Rhizobium trifolii, and the other in sterilized soil without the inoculum. In one block, the two halves of the clone remained connected, while in the other block, the two halves were severed. For all measured characters there were no significant differences between connected and severed clones. Two responses to the presence of Rhizobium were detected. First, the half clone with Rhizobium grew faster and produced more leaves, longer stolons, more new ramets, and had a greater dry weight than the other half of the same clone, either connected or severed, growing without Rhizobium. Secondly, there was a significant increase in the percent branching of nodes along the main stolon, thus altering the form of the half clone growing with Rhizobium; other within-clone characteristics did not change. These responses are discussed in the context of the ecological and evolutionary benefits and costs of integrating environmental differences experienced by the same clone.
Differential activity of acid phosphatases from the endosperm and haustorium of date palm (Phoenix dactyliferd) seeds
Authors: Sekhar K. N. Chandra , DeMason Darleen A.
Published: November 2015

The acid phosphatase (APase) activity in different parts of ungerminated and germinated seeds of date palm (Phoenix dactylifera L.) was investigated by enzyme assays and on polyacrylamide native isoelectric focusing gels. In the ungerminated seed, APase activity was detected in both the endosperm and the embryo, but the activity was greater in the endosperm. During seedling growth, enzyme activity in the developing haustorium and in the digesting endosperm was 10–15 times greater than that in dry seeds. The APases of the endosperm were different from those of the haustorium: (i) the molecular mass of the enzyme from the endosperm was approximately 52 000 while that of the haustorium was approximately 21 500; (ii) the pH optimum of the APases from the haustorium was 5.0, while it was between 5.0 and 6.5 for those of the digesting endosperm; and (iii) the endosperm contained 6 isoenzymes of pI 3.6–4.3, whereas the haustorium contained 14 isoenzymes with pIs ranging from 5.3 to 6.8. These observations suggest that phosphate metabolism in the endosperm is independent of that in the haustorium and that the APases for endosperm phosphate mobilization are not secreted by the embryo or the haustorium, but instead are stored in the endosperm.
The development of proanthocyanidins (condensed tannins) and other phenolics in bark of Pseudotsuga menziesii
Authors: Stafford Helen A. , Smith Emily C. , Weider Rosellen M.
Published: November 2015

The development and heterogeneity of proanthocyanidins in bark tissue of Pseudotsuga menziesii Franco (Douglas-fir) were analyzed chemically in extracts by means of the butanol–HCl reagent and histochemically with freehand sections by the nitroso reagent. About twice as much proanthocyanidin on a dry weight basis was found in the bark of mature hypocotyls as in the bark from 1- to 4-year-old stems and increment cores from 80-year-old trees. The proanthocyanidins were widely distributed in the vacuoles of epidermal cells, phellem, and the vascular cambial zone, but were randomly distributed in parenchyma cells within the phloem and the cortex. Only procyanidins were found in young, growing tissues, in parenchyma cells in the secondary phloem, in the vascular cambial zone, and in the bark of 80-year-old trees. Prodelphinidins were found in addition to procyanidins in the bark of 6-month-old hypocotyls and 1.5- to 4-year-old plants, possibly only in the cortical and phellem (cork) cells. Comparisons were made with nitroso reagent positive products in needles.
Extraction of DNA from Basidiomycetes for ribosomal DNA hybridizations
Authors: Rogers Scott O. , Rehner Stephen , Bledsoe Caroline , Mueller George J. , Ammirati Joe. F.
Published: November 2015

We describe a method for extracting high molecular weight DNA from milligram amounts of fungus specimens. DNA extracted from 1 – 100 mg of fresh, air-dried, or lyophilized tissue was sufficient for 1–50 Southern hybridizations. Typical yields were 1 – 10 nanograms (ng) of DNA per milligram of starting material for fresh and air-dried samples, and 50–500 ng/mg for lyophilized samples. Of the 78 samples from 63 species of saprobic and ectomycorrhizal Basidiomycetes, all but one yielded measurable amounts of nucleic acids. The DNA was used for restriction enzyme ribosomal DNA hybridizations. While most species showed similarities in the genic regions, significant size variation was seen in the intergenic regions, in most cases allowing for distinction between samples at the species level.
Regioselective addition–elimination of Morita–Baylis–Hillman adducts with 2-naphthol or phenol catalyzed by functionalized ionic liquids: a direct strategy to construct functional alkenes
Authors: Zhang Chuan-Bao , Zhang Jun , Hu Wei-Qiang , Cui Yan-Su , Liu Yong , Fu Ji-Ya , Ding Tao
Published: November 2015

A highly regioselective addition–elimination of Morita–Baylis–Hillman adducts promoted by base ionic liquids (0.5 mol%) was reported to afford a variety of functional alkenes in excellent yields (up to 99%). This protocol provides a new method to access functional alkenes directly. Recycled base ionic liquids could be reused at least five times and the isolated yield of the product was almost consistent after five runs.
Propagation of a strike-slip plate boundary within an extensional environment: the westward propagation of the North Anatolian Fault
Authors: Le Pichon Xavier , Şengör A.M. Celâl , Kende Julia , İmren Caner , Henry Pierre , Grall Céline , Karabulut Hayrullah
Published: November 2015

We document the establishment of the Aegea–Anatolia/Eurasia plate boundary in Pliocene–Pleistocene time. Before 2 Ma, no localized plate boundary existed north of the Aegean portion of the Anatolia plate and the shear produced by the motion of Anatolia–Aegea with respect to Eurasia was distributed over the whole width of the Aegean – West Anatolian western portion. In 4.5 Ma, a shear zone comparable to the Gulf of Corinth was formed in the present Sea of Marmara. The initial extensional basins were cut by the strike-slip Main Marmara Fault system after 2.5 Ma. Shortly after, the plate boundary migrated west of the Sea of Marmara along the northern border of Aegea from the North Aegean Trough, to the Gulf of Corinth area and to the Kefalonia Fault. There, it finally linked with the northern tip of the Aegean subduction zone, completing the system of plate boundaries delimiting the Anatolia–Aegea plate. We have related the change in the distribution of shear from Miocene to Pliocene to the formation of a relatively undeforming Aegea block in Pliocene that forced the shear to be distributed over a narrow plate boundary to the north of it. We attribute the formation of this block to the northeastward progression of the oceanic Ionian slab. We propose that the slab cuts the overlying lithosphere from asthenospheric sources and induces a shortening environment over it.
THE EFFECTS OF FINANCIAL DEVELOPMENT ON INVESTMENT IN TURKEY
Authors: BALCILAR MEHMET , ÇIFTÇIOĞLU SERHAN , GÜNGÖR HASAN
Published: November 2015

Analyzing financial development and investment in Turkey between 1960 and 2008, this paper illustrates how financial development affects investment decisions in a dynamic model of the firm under financial frictions. A composite index is constructed of three alternative financial development measures. The bounds testing approach was used to test for the existence of long-run levels relationships and long-run levels relationships were estimated using the autoregressive distributed lag method. Both short- and long-run causality tests were performed. Results indicate that financial development, budget balance, and total credit to the private sector positively and significantly affect investment.
Leadership Lessons from Managing Multinational Project Teams
Authors: Asgary Nader , Thamhain Hans
Published: November 2015

The challenges of managing culturally diverse and globally dispersed project teams are examined in a field study of multinational product developments. Our objectives are to improve the understanding of the: (i) dynamics and interaction of culturally diverse project teams and (ii) influences of managerial leadership on performance. Special focus is on complex, technology-based, geographically dispersed project environments.

The findings provide insight into the business processes, organizational conditions and managerial leadership style most conducive to high team performance in complex and culturally diverse project environments. The paper suggests a framework for assessing leadership effectiveness and makes recommendations for building high-performance multinational project teams.
The number of alignments between two DNA sequences
Authors: Andrade Helena , Nieto Juan J. , Torres Angela
Published: November 2015

We consider two DNA sequences and compare both sequences. One of the crucial issues in bioinformatics is to measure the similarity of two DNA sequences. To this purpose one has to consider different alignments between both sequences. The number of alignments grows very rapidly with the length of the sequences. In this paper we give exact, explicit and computable formulas for the number of different possible alignments and for some classes of reduced alignments. We provide a new insight into the theory of DNA sequence alignment.
Modeling of information images dynamics through the communicative field method
Authors: Petukhov Alexandr Y. , Polevaya S. A.
Published: November 2015

This work presents a formalized description of information and communicative interactions of individuals on the basis of the communicative field (CF) method. It also contains explication of the possibility to create model of information and communication interactions, which is able to illustrate both interactions between two and more individuals. Methods and approaches which are suggested in this paper can correctly simulate the processes of distortion and generation of information images (IIs) with information and communication social interaction. Expansion and addition of IIs theory in terms of the transmission of information between individuals allows us to speak about the space of IIs. This space helps to explain a number of characteristic phenomena of human thinking.
Computerized Adaptive Diagnosis and Testing of Mental Health Disorders
Authors: Gibbons Robert D. , Weiss David J. , Frank Ellen , Kupfer David
Published: November 2015

In this review we explore recent developments in computerized adaptive diagnostic screening and computerized adaptive testing for the presence and severity of mental health disorders such as depression, anxiety, and mania. The statistical methodology is unique in that it is based on multidimensional item response theory (severity) and random forests (diagnosis) instead of traditional mental health measurement based on classical test theory (a simple total score) or unidimensional item response theory. We show that the information contained in large item banks consisting of hundreds of symptom items can be efficiently calibrated using multidimensional item response theory, and the information contained in these large item banks can be precisely extracted using adaptive administration of a small set of items for each individual. In terms of diagnosis, computerized adaptive diagnostic screening can accurately track an hour-long face-to-face clinician diagnostic interview for major depressive disorder (as an example) in less than a minute using an average of four questions with unprecedented high sensitivity and specificity. Directions for future research and applications are discussed.
ADAM Proteases and Gastrointestinal Function
Authors: Jones Jennifer C. , Rustagi Shelly , Dempsey Peter J.
Published: November 2015

A disintegrin and metalloproteinases (ADAMs) are a family of cell surface proteases that regulate diverse cellular functions, including cell adhesion, migration, cellular signaling, and proteolysis. Proteolytically active ADAMs are responsible for ectodomain shedding of membrane-associated proteins. ADAMs rapidly modulate key cell signaling pathways in response to changes in the extracellular environment (e.g., inflammation) and play a central role in coordinating intercellular communication within the local microenvironment. ADAM10 and ADAM17 are the most studied members of the ADAM family in the gastrointestinal tract. ADAMs regulate many cellular processes associated with intestinal development, cell fate specification, and the maintenance of intestinal stem cell/progenitor populations. Several signaling pathway molecules that undergo ectodomain shedding by ADAMs [e.g., ligands and receptors from epidermal growth factor receptor (EGFR)/ErbB and tumor necrosis factor α (TNFα) receptor (TNFR) families] help drive and control intestinal inflammation and injury/repair responses. Dysregulation of these processes through aberrant ADAM expression or sustained ADAM activity is linked to chronic inflammation, inflammation-associated cancer, and tumorigenesis.
JAK inhibition using tofacitinib for inflammatory bowel disease treatment: a hub for multiple inflammatory cytokines
Authors: Danese Silvio , Grisham Matthew , Hodge Jennifer , Telliez Jean-Baptiste
Published: November 2015

The inflammatory diseases ulcerative colitis and Crohn's disease constitute the two main forms of inflammatory bowel disease (IBD). They are characterized by chronic, relapsing inflammation of the gastrointestinal tract, significantly impacting on patient quality of life and often requiring prolonged treatment. Existing therapies for IBD are not effective for all patients, and an unmet need exists for additional therapies to induce and maintain remission. Here we describe the mechanism of action of the Janus kinase (JAK) inhibitor, tofacitinib, for the treatment of IBD and the effect of JAK inhibition on the chronic cycle of inflammation that is characteristic of the disease. The pathogenesis of IBD involves a dysfunctional response from the innate and adaptive immune system, resulting in overexpression of multiple inflammatory cytokines, many of which signal through JAKs. Thus JAK inhibition allows multiple cytokine signaling pathways to be targeted and is expected to modulate the innate and adaptive immune response in IBD, thereby interrupting the cycle of inflammation. Tofacitinib is an oral, small molecule JAK inhibitor that is being investigated as a targeted immunomodulator for IBD. Clinical development of tofacitinib and other JAK inhibitors is ongoing, with the aspiration of providing new treatment options for IBD that have the potential to deliver prolonged efficacy and clinically meaningful patient benefits.
MCPIP1 mediates silica-induced cell migration in human pulmonary fibroblasts
Authors: Liu Haijun , Dai Xiaoniu , Cheng Yusi , Fang Shencun , Zhang Yingming , Wang Xingang , Zhang Wei , Liao Hong , Yao Honghong , Chao Jie
Published: November 2015

Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO2). Phagocytosis of SiO2 in the lungs initiates an inflammatory cascade that results in fibroblast proliferation and migration followed by fibrosis. According to previous data from our laboratory, monocyte chemotactic protein-1 (MCP-1) plays a critical role in fibroblast proliferation and migration in conventional two-dimensional (2D) monolayer cultures. The present study aimed to explore the downstream cascade of MCP-1 in both 2D and three-dimensional (3D) cell culture models of silicosis. Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following: 1) SiO2 treatment induces expression of MCP-1-induced protein (MCPIP1) in a time- and dose-dependent manner in both 2D and 3D cultures; 2) the MAPK and phosphatidylinositol-3-kinase (PI3K)/Akt pathways are involved in SiO2-induced MCPIP1 expression; and 3) MCPIP1 induction mediates the SiO2-induced increase in cell migration in both 2D and 3D cultures. The effect of MCP-1 in silicosis occurs mainly through MCPIP1, which, in turn, mediates the observed SiO2-induced increase in pulmonary fibroblast migration. However, the time frame for MCPIP1 induction differed between 2D and 3D cultures, indicating that, compared with conventional 2D cell culture systems, 3D culture may be useful for analyses of fibroblast physiology under conditions that more closely resemble in vivo environments. Our study determined the link between fibroblast-derived MCPIP1 and SiO2-induced cell migration, and this finding provides novel evidence of the potential of MCPIP1 in the development of novel therapeutic strategies for silicosis.
Human insulin dynamics in women: a physiologically based model
Authors: Weiss Michael , Tura Andrea , Kautzky-Willer Alexandra , Pacini Giovanni , D'Argenio David Z.
Published: November 2015

Currently available models of insulin dynamics are mostly based on the classical compartmental structure and, thus, their physiological utility is limited. In this work, we describe the development of a physiologically based model and its application to data from 154 patients who underwent an insulin-modified intravenous glucose tolerance test (IM-IVGTT). To determine the time profile of endogenous insulin delivery without using C-peptide data and to evaluate the transcapillary transport of insulin, the hepatosplanchnic, renal, and peripheral beds were incorporated into the circulatory model as separate subsystems. Physiologically reasonable population mean estimates were obtained for all estimated model parameters, including plasma volume, interstitial volume of the peripheral circulation (mainly skeletal muscle), uptake clearance into the interstitial space, hepatic and renal clearance, as well as total insulin delivery into plasma. The results indicate that, at a population level, the proposed physiologically based model provides a useful description of insulin disposition, which allows for the assessment of muscle insulin uptake.
Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats
Authors: Walsh Kathryn R. , Kuwabara Jill T. , Shim Joon W. , Wainford Richard D.
Published: November 2015

Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension.
Remote effects of acute kidney injury in a porcine model
Authors: Gardner David S. , De Brot Simone , Dunford Louise J. , Grau-Roma Llorenc , Welham Simon J. M. , Fallman Rebecca , O'Sullivan Saoirse E. , Oh Weng , Devonald Mark A. J.
Published: November 2015

Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g., AST:ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca2+] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.
Exercise training normalizes renal blood flow responses to acute hypoxia in experimental heart failure: role of the α1-adrenergic receptor
Authors: Pügge Carolin , Mediratta Jai , Marcus Noah J. , Schultz Harold D. , Schiller Alicia M. , Zucker Irving H.
Published: November 2015

Recent data suggest that exercise training (ExT) is beneficial in chronic heart failure (CHF) because it improves autonomic and peripheral vascular function. In this study, we hypothesized that ExT in the CHF state ameliorates the renal vasoconstrictor responses to hypoxia and that this beneficial effect is mediated by changes in α1-adrenergic receptor activation. CHF was induced in rabbits. Renal blood flow (RBF) and renal vascular conductance (RVC) responses to 6 min of 5% isocapnic hypoxia were assessed in the conscious state in sedentary (SED) and ExT rabbits with CHF with and without α1-adrenergic blockade. α1-adrenergic receptor expression in the kidney cortex was also evaluated. A significant decline in baseline RBF and RVC and an exaggerated renal vasoconstriction during acute hypoxia occurred in CHF-SED rabbits compared with the prepaced state ( P < 0.05). ExT diminished the decline in baseline RBF and RVC and restored changes during hypoxia to those of the prepaced state. α1-adrenergic blockade partially prevented the decline in RBF and RVC in CHF-SED rabbits and eliminated the differences in hypoxia responses between SED and ExT animals. Unilateral renal denervation (DnX) blocked the hypoxia-induced renal vasoconstriction in CHF-SED rabbits. α1-adrenergic protein in the renal cortex of animals with CHF was increased in SED animals and normalized after ExT. These data provide evidence that the acute decline in RBF during hypoxia is caused entirely by the renal nerves but is only partially mediated by α1-adrenergic receptors. Nonetheless, α1-adrenergic receptors play an important role in the beneficial effects of ExT in the kidney.
Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults
Authors: DeVan Allison E. , Johnson Lawrence C. , Brooks Forrest A. , Evans Trent D. , Justice Jamie N. , Cruickshank-Quinn Charmion , Reisdorph Nichole , Bryan Nathan S. , McQueen Matthew B. , Santos-Parker Jessica R. , Chonchol Michel B. , Bassett Candace J. , Sindler Amy L. , Giordano Tony , Seals Douglas R.
Published: November 2015

Insufficient nitric oxide (NO) bioavailability plays an important role in endothelial dysfunction and arterial stiffening with aging. Supplementation with sodium nitrite, a precursor of NO, ameliorates age-related vascular endothelial dysfunction and arterial stiffness in mice, but effects on humans, including the metabolic pathways altered, are unknown. The purpose of this study was to determine the safety, feasibility, and efficacy of oral sodium nitrite supplementation for improving vascular function in middle-aged and older adults and to identify related circulating metabolites. Ten weeks of sodium nitrite (80 or 160 mg/day, capsules, TheraVasc; randomized, placebo control, double blind) increased plasma nitrite acutely (5- to 15-fold, P < 0.001 vs. placebo) and chronically ( P < 0.10) and was well tolerated without symptomatic hypotension or clinically relevant elevations in blood methemoglobin. Endothelial function, measured by brachial artery flow-mediated dilation, increased 45-60% vs. baseline ( P < 0.10) without changes in body mass or blood lipids. Measures of carotid artery elasticity (ultrasound and applanation tonometry) improved (decreased β-stiffness index, increased cross-sectional compliance, P < 0.05) without changes in brachial or carotid artery blood pressure. Aortic pulse wave velocity was unchanged. Nitrite-induced changes in vascular measures were significantly related to 11 plasma metabolites identified by untargeted analysis. Baseline abundance of multiple metabolites, including glycerophospholipids and fatty acyls, predicted vascular changes with nitrite. This study provides evidence that sodium nitrite supplementation is well tolerated, increases plasma nitrite concentrations, improves endothelial function, and lessens carotid artery stiffening in middle-aged and older adults, perhaps by altering multiple metabolic pathways, thereby warranting a larger clinical trial.
Abnormal cell-intrinsic and network excitability in the neocortex of serotonin-deficient Pet-1 knockout mice
Authors: Puzerey Pavel A. , Kodama Nathan X. , Galán Roberto F.
Published: November 2015

Neurons originating from the raphe nuclei of the brain stem are the exclusive source of serotonin (5-HT) to the cortex. Their serotonergic phenotype is specified by the transcriptional regulator Pet-1, which is also necessary for maintaining their neurotransmitter identity across development. Transgenic mice in which Pet-1 is genetically ablated ( Pet-1−/−) show a dramatic reduction (∼80%) in forebrain 5-HT levels, yet no investigations have been carried out to assess the impact of such severe 5-HT depletion on the function of target cortical neurons. Using whole cell patch-clamp methods, two-dimensional (2D) multielectrode arrays (MEAs), 3D morphological neuronal reconstructions, and animal behavior, we investigated the impact of 5-HT depletion on cortical cell-intrinsic and network excitability. We found significant changes in several parameters of cell-intrinsic excitability in cortical pyramidal cells (PCs) as well as an increase in spontaneous synaptic excitation through 5-HT3 receptors. These changes are associated with increased local network excitability and oscillatory activity in a 5-HT2 receptor-dependent manner, consistent with previously reported hypersensitivity of cortical 5-HT2 receptors. PC morphology was also altered, with a significant reduction in dendritic complexity that may possibly act as a compensatory mechanism for increased excitability. Consistent with this interpretation, when we carried out experiments with convulsant-induced seizures to asses cortical excitability in vivo, we observed no significant differences in seizure parameters between wild-type and Pet-1−/− mice. Moreover, MEA recordings of propagating field potentials showed diminished propagation of activity across the cortical sheath. Together these findings reveal novel functional changes in neuronal and cortical excitability in mice lacking Pet-1.
Can Chronic Nitric Oxide Inhibition Improve Liver and Renal Dysfunction in Bile Duct Ligated Rats?
Authors: Mahmoud Mona Fouad , Zakaria Sara , Fahmy Ahmed
Published: November 2015

The aims of the present work were to study the effects of chronic NO inhibition on liver cirrhosis and to analyze its relationship with liver and kidney damage markers. Two inhibitors of NO synthesis (inducible NO synthase (iNOS) inhibitor, aminoguanidine (AG), and nonselective NOS inhibitor, L-nitroarginine methyl ester (L-NAME)) were administered for 6 weeks to bile duct ligated (BDL) rats 3 days after surgery. The present study showed that BDL was associated with liver injury and renal impairment. BDL increased liver NO content and myeloperoxidase (MPO) activity. This was corroborated by increased oxidative stress, TNF-α, TGF-1β, and MMP-13 genes overexpression. Although both drugs reduced NO synthesis and TNF-αgene overexpression, only AG improved renal dysfunction and liver damage and reduced liver oxidative stress. However, L-NAME exacerbated liver and renal dysfunction. Both drugs failed to modulate TGF-1βand MMP-13 genes overexpression. In conclusion, inhibition of NO production by constitutive nitric oxide synthase (cNOS) plays a crucial role in liver injury and renal dysfunction while inhibition of iNOS by AG has beneficial effect. TNF-αis not the main cytokine responsible for liver injury in BDL model. Nitric oxide inhibition did not stop the progression of cholestatic liver damage.
No Polymorphism inPlasmodium falciparum K13Propeller Gene in Clinical Isolates from Kolkata, India
Authors: Chatterjee Moytrey , Ganguly Swagata , Saha Pabitra , Bankura Biswabandhu , Basu Nandita , Das Madhusudan , Guha Subhasish K. , Maji Ardhendu K.
Published: November 2015

Molecular markers associated with artemisinin resistance inPlasmodium falciparumare yet to be well defined. Recent studies showed that polymorphisms inK13gene are associated with artemisinin resistance. The present study was designed to know the pattern of polymorphisms in propeller region ofK13gene among the clinical isolates collected from urban Kolkata after five years of ACT implementation. We collected 59 clinical isolates from urban Kolkata and sequenced propeller region ofK13gene in 51 isolates successfully. We did not find any mutation in any isolate. All patients responded to the ACT, a combination of artesunate + sulphadoxine-pyrimethamine. The drug regimen is still effective in the study area and there is no sign of emergence of resistance against artemisinin as evidenced by wild genotype ofK13gene in all isolates studied.
Application of Recycled Zero‐Valent Iron Nanoparticle to the Treatment of Wastewater Containing Nitrobenzene
Authors: Lee Heon , Kim Byung-Hoon , Park Young-Kwon , Kim Sun-Jae , Jung Sang-Chul
Published: November 2015

Zero‐valent iron (ZVI) was synthesized using iron oxide, a byproduct of pickling line at a steel work. ZVI with a mean particle size of 500 nm was synthesized. The reaction activity of the synthesized ZVI was much higher than commercial ZVI. When applied to the decomposition of nitrobenzene (NB), the ZVI particles underwent corrosion and passivation oxide film formation, resulting in particle size decrease. The NB decomposition rate increased with increasing ZVI dosage level and with decreasing pH. The solution pH increased monotonously with increasing reaction duration, whereas the aniline concentration showed a maximum at 50 min. Based on the GC/MS analysis, NB is presumed to be reduced into aniline via reductive intermediates such as azobenzene and azoxybenzene. When combined with a subsequent biological process, the synthesized ZVI will be able to decompose NB in wastewater effectively.
Characterization and Properties of Activated Carbon Prepared from Tamarind Seeds by KOH Activation for Fe(III) Adsorption from Aqueous Solution
Authors: Mopoung Sumrit , Moonsri Phansiri , Palas Wanwimon , Khumpai Sataporn
Published: November 2015

This research studies the characterization of activated carbon from tamarind seed with KOH activation. The effects of 0.5 : 1–1.5 : 1 KOH : tamarind seed charcoal ratios and 500–700°C activation temperatures were studied. FTIR, SEM‐EDS, XRD, and BET were used to characterize tamarind seed and the activated carbon prepared from them. Proximate analysis, percent yield, iodine number, methylene blue number, and preliminary test of Fe(III) adsorption were also studied. Fe(III) adsorption was carried out by 30 mL column with 5–20 ppm Fe(III) initial concentrations. The percent yield of activated carbon prepared from tamarind seed with KOH activation decreased with increasing activation temperature and impregnation ratios, which were in the range from 54.09 to 82.03 wt%. The surface functional groups of activated carbon are O–H, C=O, C–O, –CO3, C–H, and Si–H. The XRD result showed high crystallinity coming from a potassium compound in the activated carbon. The main elements found in the activated carbon by EDS are C, O, Si, and K. The results of iodine and methylene blue adsorption indicate that the pore size of the activated carbon is mostly in the range of mesopore and macropore. The average BET pore size and BET surface area of activated carbon are 67.9764 Å and 2.7167 m2/g, respectively. Finally, the tamarind seed based activated carbon produced with 500°C activation temperature and 1.0 : 1 KOH : tamarind seed charcoal ratio was used for Fe(III) adsorption test. It was shown that Fe(III) was adsorbed in alkaline conditions and adsorption increased with increasing Fe(III) initial concentration from 5 to 20 ppm with capacity adsorption of 0.0069–0.019 mg/g.