bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosis dysregulates MMP/TIMP balance to drive rapid cavitation and unrestrained bacterial proliferation
Authors: Kübler André , Luna Brian , Larsson Christer , Ammerman Nicole C , Andrade Bruno B , Orandle Marlene , Bock Kevin W , Xu Ziyue , Bagci Ulas , Mollura Daniel J , Marshall John , Burns Jay , Winglee Kathryn , Ahidjo Bintou Ahmadou , Cheung Laurene S , Klunk Mariah , Jain Sanjay K , Kumar Nathella Pavan , Babu Subash , Sher Alan , Friedland Jon S , Elkington Paul TG , Bishai William R 
Published: September 2014

AbstractActive tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP‐1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human‐like cavities (100% by day 28), with resultant bacillary burdens (>107 CFU/g) far greater than those found in matched granulomatous tissue (105 CFU/g). Using a novel, breath‐hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R2 = 0.6356, p < 0.0001). We demonstrated that the expression of interstitial collagenase (MMP‐1) was specifically greater in cavitary compared to granulomatous lesions (p < 0.01), and that TIMP‐3 significantly decreased at the cavity surface. Our findings demonstrated that an MMP‐1/TIMP imbalance is associated with the progression of consolidated regions to cavities containing very high bacterial burdens. Our model provided mechanistic insight, correlating with human disease at the pathological, microbiological and molecular levels. It also provided a strategy to investigate therapeutics in the context of complex TB pathology. We used these findings to predict a MMP/TIMP balance in active TB and confirmed this in human plasma, revealing the potential of MMP/TIMP levels as key components of a diagnostic matrix aimed at distinguishing active from latent TB (PPV = 92.9%, 95% CI 66.1–99.8%, NPV = 85.6%; 95% CI 77.0–91.9%). Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd
Aryl hydrocarbon receptor knock‐out exacerbates choroidal neovascularization via multiple pathogenic pathways
Authors: Choudhary Mayur , Kazmin Dmitri , Hu Peng , Thomas Russell S , McDonnell Donald P , Malek Goldis 
Published: September 2014

AbstractThe aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age‐related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR−/− and wild‐type (wt) mice, using high‐throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD‐related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR−/− mice and found that they measured significantly larger in area and volume compared to age‐matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium‐binding adaptor molecule 1‐positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock‐down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock‐down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor‐β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Angiogenesis is inhibitory for mammalian digit regeneration
Authors: Yu Ling , Yan Mingquan , Simkin Jennifer , Ketcham Paulina D. , Leininger Eric , Han Manjong , Muneoka Ken 
Published: September 2014

AbstractThe regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti‐angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551–559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation. Treating the amputation wound with vascular endothelial growth factor enhances angiogenesis but inhibits regeneration. We next tested bone morphogenetic protein 9 (BMP9), another known mediator of angiogenesis, and found that BMP9 is also a potent inhibitor of digit tip regeneration. BMP9 induces Vegfa expression in the digit stump suggesting that regenerative failure is mediated by enhanced angiogenesis. Finally, we show that BMP9 inhibition of regeneration is completely rescued by treatment with pigment epithelium‐derived factor. These studies show that precocious angiogenesis is inhibitory for regeneration, and provide compelling evidence that the regulation of angiogenesis is a critical factor in designing therapies aimed at stimulating mammalian regeneration.
On the use of European and American building codes with low‐strength mortars
Authors: Duplan François , Abou‐Chakra Ariane , Turatsinze Anaclet , Escadeillas Gilles , Brûlé Stéphane , Javelaud Emmanuel , Massé Frédéric 
Published: September 2014

AbstractThe standard European building specifications, grouped in a nine‐volume Eurocode, describe different approaches for determining the properties of commonly used building materials such as steel, aluminium, concrete, etc.The American Concrete Institute (ACI) also offers different reports concerning concrete structures (ACI 318R), lightweight concrete (ACI 213R) and the long‐term mechanical behaviour (ACI 209R) of concrete. Those reports, used as building codes, are applicable when the properties and composition of the material respect various criteria.All those materials that do not meet the scope criteria of Eurocode 2 or ACI reports because of their composition, property values or application cannot be used in the design of structures with those building codes. Regarding cement‐based materials, concretes and mortars whose compressive strength is lower than the minima might not be useful for structures; however, they present an interesting potential for applications such as infrastructure materials, slabs‐on‐ground, etc. When designing structures and infrastructures in those materials, the accuracy of any formula offered by those building codes should be checked before being used.This article compares experimental measurements and predictive formulas for the engineering properties (compressive and tensile strengths, modulus of elasticity). The results show that the addition of specific aggregates with low stiffness and strength modifies the relation between those engineering properties, thus reducing the accuracy of some of the predictive formulas suggested in ACI reports or Eurocodes.
Thin‐walled shell structures made of textile‐reinforced concrete
Authors: Scholzen Alexander , Chudoba Rostislav , Hegger Josef 
Published: September 2014

AbstractThe present paper describes a design approach for textile‐reinforced concrete (TRC) shells which reflects the interaction between normal forces and bending moments based on the cross‐sectional strength characteristics of the material determined experimentally. The influence of oblique loading on the composite strength of TRC elements with flexible reinforcement is included in a normalized interaction diagram for combined loading. As an example, the design approach is applied to the ultimate limit state assessment of a TRC shell in double curvature. Furthermore, the general applicability of the design approach is discussed in the light of the non‐linear loadbearing behaviour of TRC. Due to its strain‐hardening tensile response, stress redistributions within the shell result in loadbearing reserves. Details of the structural design and production solutions developed and applied during the realization of the TRC shell structure are described in the companion paper (Part I).
Minimum reinforcement for crack width control in restrained concrete members considering the deformation compatibility
Authors: Schlicke Dirk , Tue Nguyen Viet 
Published: September 2014

AbstractThe current design code EC2 [1] regulates the minimum reinforcement for crack width control in restrained concrete members by taking up the cracking force of the cross section. Although this concept gives straightforward results, its consistent application can lead to high reinforcement amounts with increasing member thickness. The reason is the simplifying assumption of an infinite member length neglecting the deformation compatibility.The cracking force approach was therefore empirically modified to reflect practical experience, see [2]. However, the main modification of a limited tensile strength seems particularly dubious, as the primarily affected thick members have already a strong developed tensile strength before any risk of cracking occurs at all.Finally, this circumstance leaves the structural designer with the dilemma of being either uneconomic or having no mechanical proof in a possible case of damage.However, the mechanically consistent estimation of the minimum reinforcement for crack width control can be achieved by considering the deformation compatibility of the restrained member, see [3]. With the introduction of [4], this deformation‐based design concept became state of the art for mass concrete members of hydraulic structures.This contribution presents the general application of the deformation‐based design concept due the findings of [5]. The reliability and the practicability of this approach will then be illustrated by the deformation‐based minimum reinforcement design of a trough structure.
Characterization and site-directed mutation of a novel aldo–keto reductase from Lodderomyces elongisporus NRRL YB-4239 with high production rate of ethyl (R)-4-chloro-3-hydroxybutanoate
Authors: Wang Qiuyan , Ye Tingting , Ma Zhuanzhuan , Chen Rong , Xie Tian , Yin Xiaopu 
Published: September 2014

Abstract
A novel aldo–keto reductase (LEK) from Lodderomyces elongisporus NRRL YB-4239 (ATCC 11503) was discovered by genome database mining for carbonyl reduction. LEK was overexpressed in Escherichia coli BL21 (DE3), purified to homogeneity and the catalytic properties were studied. Among the substrates, ethyl 4-chloro-3-oxobutanoate was converted to ethyl (R)-4-chloro-3- hydroxybutanoate ((R)-CHBE), an important pharmaceutical intermediate, with an excellent enantiomeric excess (e.e.) (&gt;99 %). The mutants W28A and S209G obtained by site-directed mutation were identified with much higher molar conversion yields and lower Km values. Further, the constructed coenzyme regeneration system with glucose as co-substrate resulted in a yield of 100 %, an enantioselectivity of &gt;99 %, and the calculated production rate of 56.51 mmol/L/H. These results indicated the potential of LEK for the industrial production of (R)-CHBE and other valuable chiral alcohols.
Glycosylation and subsequent malonylation of isoflavonoids in E. coli: strain development, production and insights into future metabolic perspectives
Authors: Koirala Niranjan , Pandey Ramesh Prasad , Van Thang Duong , Jung Hye Jin , Sohng Jae Kyung 
Published: September 2014

Abstract
Genistin and daidzein exhibit a protective effect on DNA damage and inhibit cell proliferation. Glycosylation and malonylation of the compounds increase water solubility and stability. Constructed pET15b-GmIF7GT and pET28a-GmIF7MAT were used for the transformation of Escherichia coli and bioconversion of genistein and daidzein. To increase the availability of malonyl-CoA, a critical precursor of GmIF7MAT, genes for the acyl-CoA carboxylase α and β subunits (nfa9890 and nfa9940), biotin ligase (nfa9950), and acetyl-CoA synthetase (nfa3550) from Nocardia farcinia were also introduced. Thus, the isoflavonoids were glycosylated at position 7 by 7-O-glycosyltranferase and were further malonylated at position 6″ of glucose by malonyl-CoA: isoflavone 7-O-glucoside-6″-O-malonyltransferase both from Glycine max. Engineered E. coli produced 175.7 µM (75.90 mg/L) of genistin and 14.2 µM (7.37 mg/L) genistin 6″-O-malonate. Similar conditions produced 162.2 µM (67.65 mg/L) daidzin and 12.4 µM (6.23 mg/L) daidzin 6″-O-malonate when 200 µM of each substrate was supplemented in the culture. Based on our findings, we speculate that isoflavonoids and their glycosides may prove useful as anticancer drugs with added advantage of increased solubility, stability and bioavailability.
The effect of polyhexamethylene guanidine hydrochloride (PHMG) derivatives introduced into polylactide (PLA) on the activity of bacterial enzymes
Authors: Walczak Maciej , Richert Agnieszka , Burkowska-But Aleksandra 
Published: September 2014

Abstract
The present study was aimed at investigating bactericidal properties of polylactide (PLA) films containing three different polyhexamethylene guanidine hydrochloride (PHMG) derivatives and effect of the derivatives on extracellular hydrolytic enzymes and intracellular dehydrogenases. All PHMG derivatives had a slightly stronger bactericidal effect on Staphylococcus aureus than on E. coli but only PHMG granular polyethylene wax (at the concentration of at least 0.6 %) has a bactericidal effect. PHMG derivatives introduced into PLA affected the activity of microbial hydrolases to a small extent. This means that the introduction of PHMG derivatives into PLA will not reduce its enzymatic biodegradation significantly. On the other hand, PHMG derivatives introduced into PLA strongly affected dehydrogenases activity in S. aureus than in E. coli.
Human Psychophysical Functions, an Update: Methods for Identifying their form; Estimating their Parameters; and Evaluating the Effects of Important Predictors
Authors: Kornbrot Diana E. 
Published: September 2014

Stevens’ power law for the judgments of sensation has a long history in psychology and is used in many psychophysical investigations of the effects of predictors such as group or condition. Stevens’ formulation Ψ=aPn\documentclass[12pt]{minimal}
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\begin{document}$$\varPsi = {aP}^{n}$$\end{document}, where Ψ\documentclass[12pt]{minimal}
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\begin{document}$$\varPsi $$\end{document} is the psychological judgment, P is the physical intensity, and n\documentclass[12pt]{minimal}
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\begin{document}$$n$$\end{document} is the power law exponent, is usually tested by plotting log (Ψ)\documentclass[12pt]{minimal}
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\begin{document}$$(\varPsi )$$\end{document} against log (P). In some, but by no means all, studies, effects on the scale parameter, a\documentclass[12pt]{minimal}
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\begin{document}$$a$$\end{document}, are also investigated. This two-parameter model is simple but known to be flawed, for at least some modalities. Specifically, three-parameter functions that include a threshold parameter produce a better fit for many data sets. In addition, direct non-linear computation of power laws often fit better than regressions of log-transformed variables. However, such potentially flawed methods continue to be used because of assumptions that the approximations are “close enough” as to not to make any difference to the conclusions drawn (or possibly through ignorance the errors in these assumptions). We investigate two modalities in detail: duration and roughness. We show that a three-parameter power law is the best fitting of several plausible models. Comparison between this model and the prevalent two parameter version of Stevens’ power law shows significant differences for the parameter estimates with at least medium effect sizes for duration.
Dietary Hyodeoxycholic Acid Exerts Hypolipidemic Effects by Reducing Farnesoid X Receptor Antagonist Bile Acids in Mouse Enterohepatic Tissues
Authors: Watanabe Shiro , Fujita Kyosuke 
Published: September 2014

AbstractMice were fed a control diet or a diet supplemented with hyodeoxycholic acid, the most abundant bile acid contained in pig bile, for 4 weeks, after which their serum and livers were collected. The contents of total fatty acids of serum and liver cholesteryl esters, and of liver triglycerides, were reduced following the administration of the hyodeoxycholic acid‐supplemented diet, which was mainly due to the reductions in the contents of monounsaturated fatty acids. Free cholesterol contents in the serum and liver were not changed by hyodeoxycholic acid administration. Hyodeoxycholic acid administration reduced the gene expression levels of sterol regulatory element binding protein 1c, acetyl‐CoA carboxylase, fatty acid synthase, and stearoyl‐CoA desaturase‐1. Hyodeoxycholic acid administration markedly changes the ratio of FXR‐antagonist/FXR‐agonist bile acids in the enterohepatic tissues of the mice (1.13 and 7.60 in hyodeoxycholic acid and control diet groups, respectively). Our findings demonstrate that hyodeoxycholic acid administration exerts the hypolipidemic effect in mice, in which downregulations of de novo lipogenesis and desaturation of saturated fatty acids are suggested to play important roles. In addition, regulation of FXR activation through the selective modification of the enterohepatic bile acid pool may be involved in the hypolipidemic effect of hyodeoxycholic acid administration.
A note on interpreting damn expressives: transferring the blame
Authors: FRAZIER LYN , DILLON BRIAN , CLIFTON CHARLES 
Published: September 2014

abstractExpressives like damn convey a negative attitude toward an entity or toward a situation. What is particularly interesting about such expressions is the looseness of the relation between their syntax, which is the syntax of normal attribute adjectives, and their interpretation (Potts 2005, 2007). An experiment on various negative expressives manipulated the placement of the expressive as a prior utterance, or inside the subject or inside an object of the verb or preposition. Experimental participants were asked what the speaker was most likely to have a negative attitude towards − the subject, the object, or the entire situation. The test items were of two types, ‘non-causal’ and ‘causal’, exemplified by The holiday is on the damn weekend and The dog is on the damn couch. In the non-causal items, the subject (holiday) cannot plausibly be taken as being responsible for the state of affairs described. However, in the causal items, the subject might be responsible for the state of affairs described. The same range of interpretations was observed for all placements of damn. The prior utterance condition (Damn. The dog is on the couch.) yielded more entire situation interpretations than the sentence-internal damn items. Overall, subject damn items yielded more subject interpretations than object damn items. However, as predicted by the hypothesis that blame would devolve on a potentially responsible agent (the culprit hypothesis), there were more subject interpretations in the causal items than in the non-causal items. The results suggest that considerable pragmatic inferencing is involved in the interpretation of expressives, consistent with a proposal that an expressive constitutes a separate speech act.
Effects of supplementation with two sources and two levels of copper on meat lipid oxidation, meat colour and superoxide dismutase and glutathione peroxidase enzyme activities in Nellore beef cattle
Authors: Correa Lísia Bertonha , Zanetti Marcus Antonio , Del Claro Gustavo Ribeiro , de Paiva Fernanda Alves , da Luz e Silva Saulo , Netto Arlindo Saran 
Published: September 2014

In the present study, thirty-five Nellore bulls were used to determine the effects of two levels and two sources (organic and inorganic) of Cu supplementation on the oxidative stability of lipids, measured by the thiobarbituric acid-reactive substance (TBARS) test, meat colour and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities. The following treatments were used: (1) control (C) – basal diet without supplementation of Cu (7 mg Cu/kg DM); (2) I10 – basal diet supplemented with 10 mg Cu/kg DM in the form of copper sulphate (inorganic form); (3) I40 – basal diet supplemented with 40 mg Cu/kg DM in the form of copper sulphate; (4) O10 – basal diet supplemented with 10 mg Cu/kg DM in the form of copper proteinate (organic form); (5) O40 – basal diet supplemented with 40 mg Cu/kg DM in the form of copper proteinate. Lipid oxidation was determined in meat samples exposed to display, modified atmosphere (MA) and vacuum packaging (VC) conditions and in liver samples using the TBARS test. These samples were also evaluated for meat discolouration after exposure to air. The activities of SOD and GSH-Px enzymes were determined in liver samples. In display, MA and VC conditions, the TBARS values of samples from animals supplemented with 40 mg Cu/kg DM were lower than those of samples from control animals. There was no effect of treatment on the colour variables (L*,a*,b*). There was also no significant effect of treatment on hepatic TBARS concentrations and GSH-Px activity. Supplementation with Cu at 40 mg/kg, regardless of the source, induced higher hepatic SOD activity compared with the control treatment. In conclusion, Cu supplementation improved the oxidative stability of lipids in samples exposed to display, MA and VC conditions, demonstrating the antioxidant effect of this mineral.