bluuebunny/crossref_metadata_2025 huggingface dataset:
Textile industry manufacturing by‐products induce human melanoma cell proliferationviaERK1/2 activation
Authors: Rizzi M. , Cravello B. , Renò F.
Published: September 2014

Objectives

Textiles used to make clothing can represent a source, often ignored, of chemicals potentially noxious to both skin and the whole organism. Among the most frequently produced potentially noxious chemical manufacturing by‐products are formaldehyde (FA), nickel (Ni) and hexavalent chromium (Cr); they are of potential clinical interest as all are known to be carcinogenic to humans and to be potent skin sensitizers. The aim of this study was to investigate,in vitro, effects of these potentially dangerous compounds on two different melanoma cell lines. In particular, attention was focused on A375P, a poorly metastatic and low invasive cell line andSK‐MEL‐28, a highly metastatic cell line.

Materials and methods

Effects of these compounds was evaluated on A375P andSK‐MEL‐28 cells.FA(1–5 × 10−5 m), NiSO4(10−6–10−3 m), K2Cr2O7(10−7–10−6 m) effects on cell proliferation were evaluated by cell counting, whileERKpathway involvement was evaluated by Western blot analysis.

Results

Low concentrations of the chemicals, covering a range that corresponds to commonly accepted limits in textile production, induced a significant increase in cell proliferation concomitant with transient activation of phosphorylatedERKexpression.

Conclusions

Data obtained suggest that increasing attention must be focused on these by‐products' potentially harmful effects in chemical manufacturing of clothes and accessories, that remain for long periods of time, in contact with human skin.
Advanced oxidation protein products and ischaemia‐modified albumin in obstructive sleep apnea
Authors: Ozben Serkan , Huseyinoglu Nergiz , Hanikoglu Ferhat , Guvenc Tolga Sinan , Yildirim Binnaz Zeynep , Cort Aysegul , Ozdem Sebahat , Ozben Tomris
Published: September 2014

Background

Several studies have shown that obstructive sleep apnea increases incidence of cardiovascular morbidity and mortality. The high systemic oxidative stress in obstructive sleep apnea has been considered as a major pathogenic mechanism leading to cardiovascular disease. Oxidative stress‐related lipid and DNA oxidation in obstructive sleep apnea have been reported in the previous studies. In contrast, there is limited and contradictory information regarding protein oxidation in obstructive sleep apnea patients such as ischaemia‐modified albumin and advanced oxidation protein products. Therefore, we aimed to investigate plasma ischaemia‐modified albumin and advanced oxidation protein products and their correlation with total oxidative status and total antioxidative capacity in the obstructive sleep apnea patients.

Methods

Plasma ischaemia‐modified albumin, advanced oxidation protein products, total oxidative status and total antioxidative capacity were measured in 25 healthy volunteers and 59 obstructive sleep apnea patients diagnosed with polysomnography.

Results

Plasma total antioxidative capacity was significantly lower (P = 0·012) and total oxidative status was significantly higher (P < 0·001) in the patients compared to the controls demonstrating increased oxidative stress in the patients. Plasma advanced oxidation protein products were significantly higher in the patients than the controls (P = 0·024). Plasma ischaemia‐modified albumin levels were not statistically different between the obstructive sleep apnea patients and controls (P = 0·74).

Conclusions

We conclude that high systemic oxidative stress in obstructive sleep apnea is reflected by increased advanced oxidation protein products without causing an increase in ischaemia‐modified albumin.
Evolutionary and ecological causes of species richness patterns in North American angiosperm trees
Authors: Qian Hong , Wiens John J. , Zhang Jian , Zhang Yangjian
Published: September 2014

Climate and evolutionary factors (e.g. diversification, time‐for‐speciation, niche conservatism) are both thought to be major drivers of species richness in regional assemblages. However, few studies have simultaneously investigated the relative effects of climate and evolutionary factors on species richness across a broad geographical extent. Here, we assess their relative effects on species richness of angiosperm trees across North America. Species richness of angiosperm trees in 1175 regional assemblages were related to climate and phylogenetic structure using a structural equation modeling (SEM) approach. Climate was quantified based on the mean temperature of the coldest month and mean annual precipitation. Evolutionary factors (time‐for‐speciation vs diversification) were inferred from phylogeny‐based measures of mean root distance, phylogenetic species variability, and net relatedness index. We found that at the continental scale, species richness is correlated with temperature and precipitation with approximately similar strength. In the SEM with net relatedness index and phylogenetic species variability and with all the 1175 quadrats, the total direct effect size of phylogenetic structure on species richness is greater than the total direct effect size of climate on species richness by a factor of 3.7. The specific patterns of phylogenetic structure (i.e. greater phylogenetic distances in more species rich regions) are consistent with the idea that time and niche conservatism drive richness patterns in North American angiosperm trees. We conclude that angiosperm tree species richness in regional assemblages in North America is more strongly related to patterns of phylogenetic relatedness than to climatic variation. The results of the present study support the idea that climatic and evolutionary explanations for richness patterns are not in conflict, and that evolutionary processes explain both the relationship between climate and richness and substantial variation in richness that is independent of climate.
Hierarchical and scale‐dependent effects of fishing pressure and environment on the structure and size distribution of parrotfish communities
Authors: Taylor Brett M. , Lindfield Steven J. , Choat J. Howard
Published: September 2014

Parrotfishes are considered to have a major influence on coral reef ecosystems through grazing the benthic biota and are also primary fishery targets in the Indo‐Pacific. Consequently, the impact of human exploitation on parrotfish communities is of prime interest. As anthropogenic and environmental factors interact across spatial scales, sampling programs designed to disentangle these are required by both ecologists and resource managers. We present a multi‐scale examination of patterns in parrotfish assemblage structure, size distribution and diversity across eight oceanic islands of Micronesia. Results indicate that correlates of assemblage structure are scale‐dependent; biogeographic distributions of species and island geomorphology hierarchically influenced community patterns across islands whereas biophysical features and anthropogenic pressure influenced community assemblage structure at the within‐island scale. Species richness and phylogenetic diversity increased with greater broad‐scale habitat diversity associated with different island geomorphologies. However, within‐island patterns of abundance and biomass varied in response to biophysical factors and levels of human influence unique to particular islands. While the effect of fishing activities on community composition and phylogenetic diversity was obscured across island types, fishing pressure was the primary correlate of mean parrotfish length at all spatial scales. Despite widespread fishery‐induced pressure on Pacific coral reefs, the structuring of parrotfish communities at broad spatial scales remains a story largely dependent on habitat. Thus, we propose better incorporation of scale‐dependent habitat effects in future assessments of overexploitation on reef fish assemblages. However, strong community‐level responses within islands necessitate an improved understanding of the phylogenetic and functional consequences of altering community structure.
Vocal Responsiveness to Interfering Sounds By a Frog From The Southern Temperate Forest, Batrachyla leptopus
Authors: Penna Mario , Toloza Jessica
Published: September 2014

Interfering sounds from biotic and abiotic origins are likely to shape the responsiveness of sound communicating animals. Among these sources of interference, interactions among acoustically active species have been studied to quite a limited extent. The vocal responses of 20 male frogs Batrachyla leptopus from the temperate austral forest in Chile were tested with conspecific calls and with the calls of two sympatric species: Batrachyla taeniata and Batrachyla antartandica, broadcast at amplitudes of 73, 79, 85, 91 and 97 dB SPL peak. Also, the vocal activity of the subjects during exposure to a 3‐min continuous broadband noise presented at 67 dB SPL RMS was monitored. The subjects gave higher responses on average to the conspecific relative to the heterospecific calls, but in most comparisons, these differences did not reach levels of significance. In addition, the vocal activity of males of B. leptopus did not increase in the presence of the continuous broadband noise. The lack of clear preferential responses for conspecific signals contrasts with the sharp selectivities that B. taeniata and B. antartandica have shown for their own calls in previous studies. Such different vocal behavior could be related to the extensive geographic overlap of B. leptopus with the two other species in the temperate austral forest, where mixed choruses of this species with each of the two congeneric taxa have been reported to occur occasionally. The lack of vocal activation in the presence of continuous noise also contrasts with the increased vocal output with which the other two taxa respond to this intrusion and is likely to result from a relatively high spontaneous vocal activity in B. leptopus.
Reduced sirolimus systemic exposure and improved bioresorbable polymer properties: new allies for the treatment of patients with coronary artery disease
Authors: Stojkovic Sinisa , Neskovic Aleksandar N. , Mehmedbegovic Zlatko , Kafedzic Srdjan , Ostojic Miodrag , Nedeljkovic Milan , Orlic Dejan , Ilisic Bojan , Ilic Ivan , Aleksic Aleksandar , Cerovic Milivoje , Nikolajevic Ivica , Vlahovic‐Stipac Alja , Stajic Zoran , Putnikovic Biljana , Hamilos Michalis
Published: September 2014

This prospective, first‐in‐man, open‐label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug‐eluting stent implantation (coated with sirolimus and bioabsorbable co‐polymer) in patients with de novo coronary artery disease (the TCD‐10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6‐month angiographic and up to 12 months clinical follow‐up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9–41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0–105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time–concentration curve, was 8.3 ng h/mL (range 6.47–28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity.
Neuronal porosome lipidome
Authors: Lewis Kenneth T. , Maddipati Krishna R. , Taatjes Douglas J. , Jena Bhanu P.
Published: September 2014

Cup‐shaped lipoprotein structures called porosomes are the universal secretory portals at the cell plasma membrane, where secretory vesicles transiently dock and fuse to release intravesicular contents. In neurons, porosomes measure ~15 nm and are comprised of nearly 40 proteins, among them SNAREs, ion channels, the Gαo G‐protein and several structural proteins. Earlier studies report the interaction of specific lipids and their influence on SNAREs, ion channels and G‐protein function. Our own studies demonstrate the requirement of cholesterol for the maintenance of neuronal porosome integrity, and the influence of lipids on SNARE complex assembly. In this study, to further understand the role of lipids on porosome structure‐function, the lipid composition of isolated neuronal porosome was determined using mass spectrometry. Using lipid‐binding assays, the affinity of porosome‐associated syntaxin‐1A to various lipids was determined. Our mass spectrometry results demonstrate the presence of phosphatidylinositol phosphates (PIP's) and phosphatidic acid (PA) among other lipids, and the enriched presence of ceramide (Cer), lysophosphatidylinositol phosphates (LPIP) and diacylglycerol (DAG). Lipid binding assays demonstrate the binding of neuronal porosome to cardiolipin, and confirm its association with PIP's and PA. The ability of exogenous PA to alter protein–protein interaction and neurotransmitter release is further demonstrated from the study.
The potential influence of morphology on the evolutionary divergence of an acoustic signal
Authors: Pitchers W. R. , Klingenberg C. P. , Tregenza T. , Hunt J. , Dworkin I.
Published: September 2014

The evolution of acoustic behaviour and that of the morphological traits mediating its production are often coupled. Lack of variation in the underlying morphology of signalling traits has the potential to constrain signal evolution. This relationship is particularly likely in field crickets, where males produce acoustic advertisement signals to attract females by stridulating with specialized structures on their forewings. In this study, we characterize the size and geometric shape of the forewings of males from six allopatric populations of the black field cricket (Teleogryllus commodus) known to have divergent advertisement calls. We sample from each of these populations using both wild‐caught and common‐garden‐reared cohorts, allowing us to test for multivariate relationships between wing morphology and call structure. We show that the allometry of shape has diverged across populations. However, there was a surprisingly small amount of covariation between wing shape and call structure within populations. Given the importance of male size for sexual selection in crickets, the divergence we observe among populations has the potential to influence the evolution of advertisement calls in this species.
Endoplasmic reticulum stress response and bone loss in experimental periodontitis in mice
Authors: Yamada H. , Nakajima T. , Domon H. , Honda T. , Yamazaki K.
Published: September 2014

Background and Objective

Endoplasmic reticulum (ER) stress is the cell response that activates the unfolded protein response (UPR) pathway in a variety of conditions, such as inflammation and bone metabolism. The UPR may be associated with the pathogenesis of periodontal disease because the disease is inflammatory in nature, and alveolar bone resorption is a characteristic feature of the disease. However, the relationship between ER stress and alveolar bone resorption observed in periodontal disease remains elusive.

Material and Methods

C57BL/6 mice were orally administered Porphyromonas gingivalis, a representative periodontopathic bacterium, in the presence or absence of a chemical chaperone, 4‐phenylbutyrate (4‐PBA). The gene expression of UPR‐related molecules and cytokines in gingival tissues were analyzed using real‐time polymerase chain reaction, and alveolar bone resorption and osteoclast numbers were evaluated histologically. The in vitro effect of 4‐PBA on the differentiation of mouse bone marrow cells induced by receptor activator of nuclear factor‐κB ligand in the presence of macrophage colony‐stimulating factor was analyzed.

Results

The gene expression levels of UPR‐related molecules and proinflammatory cytokines and alveolar bone resorption were significantly increased in P. gingivalis‐administered mice. UPR‐related gene expression and alveolar bone resorption were significantly suppressed by the administration of 4‐PBA. However, no effect of 4‐PBA was observed for proinflammatory cytokine expression in gingival tissues. Osteoclastic differentiation of bone marrow cells was also suppressed by 4‐PBA with a concomitant reduction in the gene expression of cathepsin K and tartrate‐resistant alkaline phosphatase genes.

Conclusion

ER stress induced by oral administration of P. gingivalis is involved in alveolar bone resorption independent of inflammatory cytokines in mice.
Environmental effects on the reproduction and fecundity of the introduced calcareous sponge Paraleucilla magna in Rio de Janeiro, Brazil
Authors: Lanna Emilio , Paranhos Rodolfo , Paiva Paulo C. , Klautau Michelle
Published: September 2014

The calcareous sponge Paraleucilla magna (Porifera, Calcarea) has been the subject of several studies in the last decade. It was first described along the Brazilian coast, where it is considered cryptogenic, and was subsequently found in the Mediterranean, where it is considered invasive. The wide artificial distribution of this species allows us to compare different aspects of the biology of an introduced species in different locations. Here, we analysed the effects of selected environmental parameters on the reproductive dynamics of P. magna in Rio de Janeiro (Brazil) over 18 months and compared our results with those obtained for the same species in the Mediterranean Sea. Specimens were collected monthly and analysed through histological methods. The density of reproductive elements in each month was calculated, and the effects of environmental parameters (photoperiod, precipitation, temperature, phytoplankton and bacterioplankton) were analysed using a regression tree analysis. Paraleucilla magna was reproductive throughout the study period. The densities of the reproductive elements (oocytes, embryos and larvae) showed no seasonality, and this species presented one of the highest reproductive efforts documented to date in the phylum Porifera (99.0 oocytes · mm−3; 89.0 embryos · mm−3; 319.0 larvae · mm−3). The main environmental parameters related to the reproduction of P. magna were temperature, photoperiod and bacterioplankton. Temperature was the main driver associated with the densities of oocytes and embryos, while bacterioplankton was the main driver of larvae (positive relationships). In Rio de Janeiro, larvae were present and continuously released. This strategy is different from that observed in the Mediterranean, where a larger larval output was observed but only during the summer months. Our results show that P. magna is a species with a strong invasive potential, considering its high and continuous reproductive effort. This high fecundity stimulated by high temperatures may be a key factor contributing to the growth of P. magna populations and its invasion of new areas.
Impatiens shimianensis sp. nov. (Balsaminaceae) from Sichuan, China
Authors: Luo Qiang , Wang Tong‐Jun , Zhao Li‐Hua
Published: September 2014

Impatiens shimianensis Q. Luo (Balsaminaceae), a new species from Shimian county in southwestern Sichuan province, China, is reported and its morphological characteristics are described and illustrated. Pollen grain morphology and seeds under SEM are also described. The new species is somewhat similar to I. bahanensis, I. brachycentra, I. laxiflora, I. parviflora and I. racemosa, but differs mainly by having leaf blades with white short stiff adpressed hairs; basal lobes of lateral united petals triangular, distal lobes lanceolate; and lower sepal salver‐shaped. The distinguishing characters for these six Impatiens species are given in a table.
Sacral nerve stimulation changes rectal sensitivity and biomechanical properties in patients with irritable bowel syndrome
Authors: Fassov J. , Brock C. , Lundby L. , Drewes A. M. , Gregersen H. , Buntzen S. , Laurberg S. , Krogh K.
Published: September 2014

Background

Sacral nerve stimulation (SNS) has been demonstrated to alleviate symptoms and improve quality of life in selected patients with irritable bowel syndrome (IBS). The mechanisms of action, however, remain unknown. The aim of the study was to evaluate the effects of SNS on rectal sensitivity and biomechanical properties in patients with IBS.

Methods

Twenty patients with diarrhea‐predominant (n = 11) or mixed (n = 9) IBS were treated with SNS in a controlled, randomized crossover trial. They were randomized to either 1 month of SNS (ON) or placebo (OFF) with the opposite setting for the next month. Sensory and biomechanical parameters were assessed by multimodal rectal stimulation at the end of each period. IBS‐specific symptoms were evaluated at baseline and at the end of each treatment period.

Key Results

Cold stimuli were better tolerated in the ON period (19.9 °C[±0.6]) compared to the OFF period (21.8 °C[±0.6]; p = 0.03). Significantly lower cross‐sectional areas were needed to elicit sensory responses in the ON period (1545 mm2[±95]) compared to the OFF period (1869 mm2[±92]; p = 0.015). The association between reduced sensory threshold and improvement of constipation was of borderline significance (p = 0.05). Wall stiffness was significantly lower in the ON period (192 mmHg[±10]) compared to the OFF period (234 mmHg[±10]; p = 0.004). Reduced wall stiffness was significantly associated with improved overall GSRS‐IBS symptom score (p = 0.01). Reduced sensory threshold to stretch (p = 0.02) and reduced wall stiffness (p < 0.001) were predictors of the GSRS‐IBS symptom score.

Conclusions & Inferences

SNS for diarrhea‐predominant and mixed IBS relaxes the rectal wall, while making it more sensitive to stretch and less sensitive to cold. Reduced wall stiffness and increased sensitivity to stretch are associated with improved GSRS‐IBS symptom score.
Clinical Characteristics and Predictors of Super‐Response to Cardiac Resynchronization Therapy: A Combination of Predictive Factors
Authors: YANAGISAWA SATOSHI , INDEN YASUYA , SHIMANO MASAYUKI , YOSHIDA NAOKI , FUJITA MASAYA , OHGUCHI SHIOU , ISHIKAWA SHINJI , KATO HIROYUKI , OKUMURA SATOSHI , MIYOSHI AYA , NAGAO TOMOYUKI , YAMAMOTO TOSHIHIKO , HIRAI MAKOTO , MUROHARA TOYOAKI
Published: September 2014

Background

Patients with greater improvement of cardiac function after cardiac resynchronization therapy (CRT) implantation are identified as “super‐responders.” However, it remains unclear which kind of preimplant assessments could accurately predict outcomes after CRT. Thus, we aimed to examine the essential predicting factors for super‐response to CRT, and to construct an accurate predictable model.

Methods

We retrospectively analyzed the CRT patients who underwent implantation at Nagoya University Hospital. Super‐responders are defined as those who show a relative reduction in left ventricular end‐systolic volume ≥30% after 6 months of CRT.

Results

Eighty patients (mean age, 67.8 ± 10.2 years) were included. Twenty‐two patients received upgrading procedure to CRT implantation. Six months after the implantation, 29 patients (36%) were super‐responders. Multiple logistic regression analysis shows that consistent right ventricular pacing with a previous device (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.52–34.9; P = 0.013), lack of prior history of ventricular arrhythmia (OR 5.32, 95% CI 1.52–18.6; P = 0.009), and smaller left atrial diameter (LAD) (OR 0.92, 95% CI 0.86–0.98; P = 0.014) are independent predictors for CRT super‐responders. The use of a combination of these predictive factors could increase the certainty with which a greater response to CRT is predicted and the presence of such a combination could improve prognosis.

Conclusion

Greater response to biventricular pacing occurs more frequently in patients with consistent right ventricular pacing, lack of prior history of ventricular arrhythmia, and smaller LAD. An association between patient background characteristics and a super‐response to CRT was also identified.
Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol
Authors: Hibino Satoshi , Uemura Osamu , Nagai Takuhito , Yamakawa Satoshi , Iwata Naoyuki , Ito Hidekazu , Nakano Masaru , Tanaka Kazuki
Published: September 2014

Background

This retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome.

Methods

Cyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high‐dose steroid therapy. CsA was maintained at an area under the whole blood concentration–time curve up to 4 h after dose (AUC0–4) of 1500 and 2000 ng·h/mL in steroid‐dependent nephrotic syndrome (SDNS) and steroid‐resistant nephrotic syndrome (SRNS), respectively. Ninety‐one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission.

Results

In the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid‐sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped.

Conclusions

Treatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS.
Modulation of Immune Response by RAGE and TLR4 Signalling in PBMCs of Diabetic and Non‐Diabetic Patients
Authors: Frasnelli S. C. T. , de Medeiros M. C. , Bastos A. de S. , Costa D. L. , Orrico S. R. P. , Rossa Junior C.
Published: September 2014

Diabetes is associated with increased glucose levels and accumulation of glycated products. It is also associated with impairment in the immune response, such as increased susceptibility to infections. In this study, we assessed the possible interactions between TLR4 and RAGE signalling on apoptosis and on the expression of inflammatory cytokines in PBMC from individuals with and without diabetes. PBMCs were isolated from seven diabetic patients and six individuals without diabetes and stimulated in vitro with bacterial LPS (1 μg/ml) associated or not with BSA‐AGE (200 μg/ml). This stimulation was performed for 6 h, both in the presence and in the absence of inhibitors of TLR4 (R. sphaeroides LPS, 20 μg/ml) and RAGE (blocking monoclonal antibody). Apoptosis at early and late stages was assessed by the annexin‐V/PI staining using flow cytometry. Regulation of TNF‐α and IL‐10 gene expression was determined by RT‐qPCR. PBMCs from diabetes patients tended to be more resistant apoptosis. There were no synergistic or antagonistic effects with the simultaneous activation of TLR4 and RAGE in PBMCs from either diabetes or non‐diabetes group. Activation of TLR4 is more potent for the induction of TNF‐α and IL‐10; RAGE signalling had a negative regulatory effect on TNF‐α expression induced by LPS. TLR and RAGE do not have relevant roles in apoptosis of PBMCs. The activation of TLR has greater role than RAGE in regulating the gene expression of IL‐10 and TNF‐α.
Tranilast Inhibits the Function of Cancer‐Associated Fibroblasts Responsible for the Induction of Immune Suppressor Cell Types
Authors: Ohshio Y. , Hanaoka J. , Kontani K. , Teramoto K.
Published: September 2014

Cancer‐associated fibroblasts (CAFs) are the dominant stromal component in the tumour microenvironment (TME), playing critical roles in generation of pro‐tumourigenic TME; however, their contribution to suppression of antitumour immune responses has not been fully understood. To elucidate the interaction between CAFs and immune suppressor cells, we examined whether inhibition of CAFs function would impair the induction of immune suppressor cell types in vitro. In this study, we applied an anti‐allergic and antifibrotic agent tranilast, which is used clinically, and evaluated a potential of tranilast to serve as a CAFs inhibitor. CAFs that had been isolated from E.G7 or LLC1 tumour‐bearing mice were cultured in the presence of tranilast, and thereafter, CAFs functions on the secretion of some soluble factors as well as the induction of immune suppressor cells were evaluated. As a result, tranilast inhibited the proliferation of CAFs and reduced the levels of stromal cell‐derived factor‐1, prostaglandin E2 and transforming growth factor‐β1 from CAFs in a dose‐dependent manner. On the other hand, tranilast exerted no inhibitory effects on immune cells at doses under 100 μm. The induction of regulatory T cells and myeloid‐derived suppressor cells from their progenitor cells was suppressed in the medium that CAFs had been cultured in the presence of tranilast; however, these findings were not observed when those progenitor cells were cultured in the medium containing tranilast alone. These data demonstrate that tranilast inhibits CAFs function, which is responsible for the induction of immune suppressor cells, and possesses a potential to serve as a specific CAFs inhibitor.
Race in the Color‐blind Era: Deracialization and Black Elected Officials
Authors: Johnson Lawrence
Published: September 2014

This paper reviews the emergence of Black elected officials and the deracialization concept within the literature of Blacks politics. The aim is to provide an overview of the critical issues and debates regarding Black elected officials since the Civil Rights Movement. I contend that an understanding of deracialization as an analytical construct, to assess the viability of Black elected officials and election outcomes, is clearer when examined from the perspective of structural change. Rather than just examining specific candidates and campaigns, a sociological approach that situates Black elected officials within the macro changes of society explains the contradiction of greater political representation yet persistent racial inequality. I conclude this paper with a brief discussion of how the study of deracialization as racial phenomena can be advanced through critical discourse analysis that identifies candidates within social networks of power and influence.
Personality and Creativity: The Dual Pathway to Creativity Model and a Research Agenda
Authors: Baas Matthijs , Roskes Marieke , Sligte Daniel , Nijstad Bernard A. , De Dreu Carsten K. W.
Published: September 2014

To better understand the relation between personality traits and creativity, we invoke the Dual‐Pathway to Creativity model (DPCM) that identifies two pathways to creative outcomes: (1) flexible processing of information (cognitive flexibility) and (2) persistent probing, and systematically and incrementally combining elements and possibilities (cognitive persistence). DPCM further proposes that dispositional or situational variables may influence creativity through either their effects on flexibility or persistence. Here, we propose the idea that approach‐related traits (e.g., openness to experience, extraversion, positive affectivity, and power‐motivation) may lead to greater creativity because they link to enhanced cognitive flexibility, whereas avoidance‐related traits (e.g., negative affectivity and neuroticism) under the right circumstances may lead to greater creativity because they link to enhanced cognitive persistence. Empirical support for this proposition is discussed, and a research agenda for future work on personality and creativity is set.
The inter‐kingdom volatile signal indole promotes root development by interfering with auxin signalling
Authors: Bailly Aurélien , Groenhagen Ulrike , Schulz Stefan , Geisler Markus , Eberl Leo , Weisskopf Laure
Published: September 2014

Recently, emission of volatile organic compounds (VOCs) has emerged as a mode of communication between bacteria and plants. Although some bacterial VOCs that promote plant growth have been identified, their underlying mechanism of action is unknown. Here we demonstrate that indole, which was identified using a screen for Arabidopsis growth promotion by VOCs from soil‐borne bacteria, is a potent plant‐growth modulator. Its prominent role in increasing the plant secondary root network is mediated by interfering with the auxin‐signalling machinery. Using auxin reporter lines and classic auxin physiological and transport assays we show that the indole signal invades the plant body, reaches zones of auxin activity and acts in a polar auxin transport‐dependent bimodal mechanism to trigger differential cellular auxin responses. Our results suggest that indole, beyond its importance as a bacterial signal molecule, can serve as a remote messenger to manipulate plant growth and development.
A multicenter, randomized, controlled clinical trial evaluating the use of dehydrated human amnion/chorion membrane allografts and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers
Authors: Serena Thomas E. , Carter Marissa J. , Le Lam T. , Sabo Matthew J. , DiMarco Daniel T. ,   EpiFix VLU Study Group
Published: September 2014

Venous leg ulcers produce significant clinical and economic burdens on society and often require advanced wound therapy. The purpose of this multicenter, randomized, controlled study is to evaluate the safety and efficacy of one or two applications of dehydrated human amnion/chorion membrane allograft and multilayer compression therapy vs. multilayer compression therapy alone in the treatment of venous leg ulcers. The primary study outcome was the proportion of patients achieving 40% wound closure at 4 weeks. Of the 84 participants enrolled, 53 were randomized to receive allograft and 31 were randomized to the control group of multilayer compression therapy alone. At 4 weeks, 62% in the allograft group and 32% in the control group showed a greater than 40% wound closure (p = 0.005), thus showing a significant difference between the allograft‐treated groups and the multilayer compression therapy alone group at the 4‐week surrogate endpoint. After 4 weeks, wounds treated with allograft had reduced in size a mean of 48.1% compared with 19.0% for controls. Venous leg ulcers treated with allograft had a significant improvement in healing at 4 weeks compared with multilayer compression therapy alone.
Separating Chokers From Nonchokers: Predicting Real-Life Tennis Performance Under Pressure From Behavioral Tasks That Tap Into Working Memory Functioning
Authors: Bijleveld Erik , Veling Harm
Published: September 2014

To better understand the characteristics of athletes who tend to underperform under pressure, we investigated how (a) working memory (WM) capacity and (b) responsiveness of the dopamine system shape real-life performance under pressure. We expected that athletes with smaller WM capacity or a more responsive dopamine system (as operationalized with a risk-taking measure) are especially prone to fail during decisive moments. In a sample of competitive tennis players, WM capacity was measured with the Automated Operation Span task (AOSPAN); responsiveness of the dopamine system was measured with a risk-taking measure, the Balloon Analogue Risk Task (BART). As expected, higher AOSPAN scores predicted better performance during decisive sets; higher BART scores predicted worse performance during decisive sets. These findings indicate that real-life tennis performance can be predicted from behavioral tasks that tap into WM functioning and risk taking, and suggest that the ability to effectively use WM despite pressure separates chokers from nonchokers.
Effects of Dosage, Comorbidities, and Food on Isoniazid Pharmacokinetics in Peruvian Tuberculosis Patients
Authors: Requena-Méndez Ana , Davies Geraint , Waterhouse David , Ardrey Alison , Jave Oswaldo , López-Romero Sonia Llanet , Ward Stephen A. , Moore David A. J.
Published: September 2014

Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic (PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This study aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e., biweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric methods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The mean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (
P
< 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (
C
max
) and area under the concentration-time curve from 0 to 6 h (AUC
0–6
) were 2.77 mg/liter and 9.71 mg·h/liter, respectively, for daily administration and 8.74 mg/liter and 37.8 mg·h/liter, respectively, for biweekly administration. There were no differences in the
C
max
with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with lower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during the continuation phase did not reach the
C
max
reference value. However, low levels of INH were not associated with poorer clinical outcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate any effect on PK. We were unable to demonstrate a clear relationship between the
C
max
and treatment outcome in this data set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential patient factors under program conditions.
N
-Butyl-[1-(4-Methoxy)Phenyl-9
H
-β-Carboline]-3-Carboxamide Prevents Cytokinesis in Leishmania amazonensis
Authors: Stefanello T. F. , Panice M. R. , Ueda-Nakamura T. , Sarragiotto M. H. , Auzély-Velty R. , Nakamura C. V.
Published: September 2014

Leishmaniasis, a complex of diseases caused by protozoa of the genus
Leishmania
, is endemic in 98 countries, affecting approximately 12 million people worldwide. Current treatments for leishmaniasis have many disadvantages, such as toxicity, high costs, and prolonged treatment, making the development of new treatment alternatives highly relevant. Several studies have verified the antileishmanial activity of β-carboline compounds. In the present study, we investigated the
in vitro
antileishmanial activity of
N
-butyl-[1-(4-methoxy)phenyl-9
H
-β-carboline]-3-carboxamide (β-CB) against
Leishmania amazonensis
. The compound was active against promastigote, axenic amastigote, and intracellular amastigote forms of
L. amazonensis
, exhibiting high selectivity for the parasite. Moreover, β-CB did not exhibit hemolytic or mutagenic potential. Promastigotes treated with the alkaloid presented rounding of the body cell, cell membrane projections, an increase in the number of promastigotes presenting two flagella, and parasites of abnormal phenotype, with three or more flagella and/or nuclei. Furthermore, we observed an increase in the subpopulation of cells in the G
2
/M stage of the cell cycle. Altogether, these results suggest that β-CB likely prevents cytokinesis, although it does not interfere with the duplication of cell structures. We also verified an increase in O
2
·−
production and the accumulation of lipid storage bodies. Cell membrane integrity was maintained, in addition to the absence of phosphatidylserine externalization, DNA fragmentation, and autophagosomes. Although the possibility of an apoptotic process cannot be discarded, β-CB likely exerts its antileishmanial activity through a cytostatic effect, thus preventing cellular proliferation.
In Vitro
Susceptibility of Mycobacterium tuberculosis Isolates to an Oral Carbapenem Alone or in Combination with β-Lactamase Inhibitors
Authors: Horita Yasuhiro , Maeda Shinji , Kazumi Yuko , Doi Norio
Published: September 2014

We evaluated the antituberculosis (anti-TB) activity of five β-lactams alone or in combination with β-lactamase inhibitors against 41 clinical isolates of
Mycobacterium tuberculosis
, including multidrug-resistant and extensively drug-resistant strains. Of those, tebipenem, an oral carbapenem, showed the most potent anti-TB activity against clinical isolates, with a MIC range of 0.125 to 8 μg/ml, which is achievable in the human blood. More importantly, in the presence of clavulanate, MIC values of tebipenem declined to 2 μg/ml or less.
The Diguanylate Cyclase SadC Is a Central Player in Gac/Rsm-Mediated Biofilm Formation in Pseudomonas aeruginosa
Authors: Moscoso Joana A. , Jaeger Tina , Valentini Martina , Hui Kailyn , Jenal Urs , Filloux Alain
Published: September 2014

Pseudomonas aeruginosa
is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cystic fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP) signaling pathways are both central to this phenomenon redirecting the
P. aeruginosa
population toward a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm
retS
mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the
sadC
gene does not seem to be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in
P. aeruginosa
. While this organism possesses more than 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understanding of this insulation mechanism.
Anterior capsular defect with acute anterior subcapsular cataract in herpetic keratouveitis
Authors: Arora Tarun , Sharma Namrata , Arora Supriya , Titiyal Jeewan S
Published: September 2014

A 20-year-old man presented with a recurrent episode of herpetic keratouveitis in his right eye. The patient was treated with oral acyclovir and topical steroids. One week later the patient reported a sudden diminution of vision. Slitlamp biomicroscopy revealed the presence of a central anterior capsular defect and anterior subcapsular cataract. Dosage of steroids was temporarily increased and progression of cataract monitored. Subsequently, the anterior chamber reaction decreased and steroids were tapered.
The effects of random breath testing and lowering the minimum legal drinking age on traffic fatalities in Australian states
Authors: Jiang Heng , Livingston Michael , Manton Elizabeth
Published: September 2014

Objective

This study aims to apply time series analysis techniques to examine the effects of random breath testing (RBT) on three age-specific traffic fatalities in four Australian states while considering the effects of lowering the minimum legal drinking age (MLDA).

Methods

Long-term time series of age-specific traffic crash deaths in four Australian states were used to analyse the impact of RBT implementation while considering the population growth, increase in motor vehicle registrations and the effects of lowering the MLDA.

Results

The results of intervention analysis indicate that RBT has substantially reduced traffic fatalities in all four states since it was introduced, particularly among the 17-year-olds to 20-year-olds and 21-year-olds to 30-year-olds. New South Wales received the biggest total net effect from RBT implementation on traffic deaths. By contrast, RBT produced only a modest reduction in traffic fatalities among 30-year-olds to 39-year-olds. Lowering the MLDA was associated with significant increases in traffic fatalities among 17-year-olds to 39-year-olds in Queensland and Western Australia.

Conclusions

Controlling for the declining trend in traffic fatalities, the effects of changes in the MLDA law, the implementation of RBT has generated a huge effect, preventing an estimated 5279 traffic crash deaths in four Australian states. This provides further evidence that the implementation of RBT and increases in the MLDA are effective policies for reducing traffic fatalities.
On holomorphic flows on Stein surfaces: Transversality, dicriticalness and stability
Authors: Ito T. , Scárdua B. , Yamagishi Y.
Published: September 2014

We study the classification of the pairs (N, X) where N is a Stein surface and X is a ℂ-complete holomorphic vector field with isolated singularities on N. We describe the role of transverse sections in the classification of X and give necessary and sufficient conditions on X in order to have N biholomorphic to ℂ2. As a sample of our results, we prove that N is biholomorphic to ℂ2 if H2(N, ℤ) = 0, X has a finite number of singularities and exhibits a singularity with three separatrices or, equivalently, a singularity with first jet of the form [Formula: see text] where λ1/λ2 ∈ ℚ+. We also study flows with many periodic orbits (i.e. orbits diffeomorphic to ℂ*), in a sense we will make clear, proving they admit a meromorphic first integral or they exhibit some special periodic orbit, whose holonomy map is a non-resonant nonlinearizable diffeomorphism map.
AMERICAN UNIONS AND THE ECONOMY — THE UNHEARD VOICE OF A SHRINKING SECTOR
Authors: BELLACE JANICE
Published: September 2014

Prior to the 1970s, unions in America represented nearly a third of the non-agricultural labor force with a significantly higher percentage in major manufacturing industries. Since then, union membership in the private sector has mirrored the steep decline in manufacturing jobs. Reduced numbers means greatly reduced political clout, such that unions today exercise almost no influence on national economic policy, even at a time of deep recession. From the 1980s onward, there has been a marked shift from a Keynesian macroeconomic framework toward a monetarist and liberal market model of economic policy, such that unions are viewed by many as anti-competitive in nature and as a constraint on a free market. This has further weakened their voice on policies relating to globalization. The minimal influence of unions and the lack of other mechanisms for collective employee voice have led to a weakening of policies designed to promote employment, even at a time of high unemployment. For over a decade, there have been no formal, or even regular informal tripartite discussions on employment policy matters. Moreover, even during a Democratic administration, unions have not been given a seat at the policy table.