bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular Encapsulation Enhances Cardiac Repair
Authors: Levit Rebecca D. , Landázuri Natalia , Phelps Edward A. , Brown Milton E. , García Andrés J. , Davis Michael E. , Joseph Giji , Long Robert , Safley Susan A. , Suever Jonathan D. , Lyle Alicia N. , Weber Collin J. , Taylor W. Robert
Published: October 2013

Background

Stem cells for cardiac repair have shown promise in preclinical trials, but lower than expected retention, viability, and efficacy. Encapsulation is one potential strategy to increase viable cell retention while facilitating paracrine effects.

Methods and Results

Human mesenchymal stem cells (
hMSC
) were encapsulated in alginate and attached to the heart with a hydrogel patch in a rat myocardial infarction (
MI
) model. Cells were tracked using bioluminescence (
BLI
) and cardiac function measured by transthoracic echocardiography (
TTE
) and cardiac magnetic resonance imaging (
CMR
). Microvasculature was quantified using von
W
illebrand factor staining and scar measured by
M
asson's
T
richrome. Post‐
MI
ejection fraction by
CMR
was greatly improved in encapsulated
hMSC
‐treated animals (
MI
: 34±3%,
MI
+Gel: 35±3%,
MI
+Gel+
hMSC
: 39±2%,
MI
+Gel+encapsulated
hMSC
: 56±1%; n=4 per group;
P
<0.01). Data represent mean±
SEM
. By
TTE
, encapsulated
hMSC
‐treated animals had improved fractional shortening. Longitudinal
BLI
showed greatest
hMSC
retention when the cells were encapsulated (
P
<0.05). Scar size at 28 days was significantly reduced in encapsulated
hMSC
‐treated animals (
MI
: 12±1%, n=8;
MI
+Gel: 14±2%, n=7;
MI
+Gel+
hMSC
: 14±1%, n=7;
MI
+Gel+encapsulated
hMSC
: 7±1%, n=6;
P
<0.05). There was a large increase in microvascular density in the peri‐infarct area (
MI
: 121±10, n=7;
MI
+Gel: 153±26, n=5;
MI
+Gel+
hMSC
: 198±18, n=7;
MI
+Gel+encapsulated
hMSC
: 828±56 vessels/mm
2
, n=6;
P
<0.01).

Conclusions

Alginate encapsulation improved retention of
hMSC
s and facilitated paracrine effects such as increased peri‐infarct microvasculature and decreased scar. Encapsulation of
MSCs
improved cardiac function post‐
MI
and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases.
Life cycle and damage of the root-knot nematode Meloidogyne minor on potato, Solanum tuberosum
Authors: Wesemael Wim M.L. , Taning Lirette M. , Viaene Nicole , Moens Maurice
Published: October 2013

Meloidogyne minor is a root-knot nematode reported in Belgium, Ireland, The Netherlands, Portugal, United Kingdom, Chile and the United States. It is found in sport fields and golf courses where it causes the yellow patch disease. However, M. minor has also been detected in potato fields in The Netherlands and the UK and may pose a threat for potato cultivation. Therefore, the life cycle and damage of M. minor on potato cv. Bintje were examined under controlled conditions. To assess its life cycle, young potato plants were inoculated with freshly hatched second-stage juveniles (J2). The developmental stages of M. minor were recorded at weekly intervals after inoculation until second generation J2 were detected. One week after inoculation, only vermiform juveniles were found in the roots. All juveniles were swollen after 3 weeks and the first adult females were observed. Egg masses were seen after 6 weeks together with second generation J2. The number of degree days for M. minor to complete its life cycle was calculated using a base temperature of 5°C (DD5); between 606 and 727 DD5 were needed to complete the life cycle. Damage development of M. minor on potato was examined in a pot experiment with different inoculation densities. Symptoms (galling on the tubers) were similar to those caused by M. chitwoodi and M. fallax. At initial population densities () of 10 J2 (100 cm3 soil)−1 and more, tubers showed galls. Severely damaged potato tubers were observed at (100 cm3 soil)−1 and a damage threshold of 41 J2 (100 cm3 soil)−1 was calculated. An in vitro test showed that five, commonly grown, potato cultivars were good hosts for M. minor. Based on our results, M. minor is able to develop on potato and cause severe damage at low initial population densities. Therefore, further spread of this nematode in agricultural fields should be avoided.
A new genus and species of ambush bugs from South Africa
(Hemiptera: Heteroptera: Reduviidae: Phymatinae)
Authors: RÉDEI DÁVID , JINDRA ZDENĚK
Published: October 2013

Doesburgella gen. nov. and its type species D. dilatata sp. nov. (Hemiptera: Heteroptera: Reduviidae: Phymatinae: Macrocephalini) are described from South Africa.
Description of the larva of Neuraeschna claviforcipata Martin, 1909 (Insecta: Odonata: Aeshnidae)
Authors: MARMELS JÜRG DE , NEISS ULISSES GASPAR
Published: October 2013

The ultimate stadium larva of Neuraeschna claviforcipata is described and illustrated based on an F-0 exuvia of a reared female from northern Amazonas State, Brazil. This larva differs from the other two known larvae of the genus in lacking the spiny lateral prominence of the mandible, and in having only a short spine each side of the median cleft of the prementum; labium is shorter and cercus longer. Noteworthy is the presence of a hair brush on each occipital lobe behind mesal angle of compound eye. The larva was found in a small blackwater pool with abundant leaf litter in an open, “campina”-type habitat, with sandy soil and low, bushy vegetation.
Potential Utilization of Specific Attenuation for Rainfall Estimation, Mitigation of Partial Beam Blockage, and Radar Networking
Authors: Ryzhkov Alexander , Diederich Malte , Zhang Pengfei , Simmer Clemens
Published: October 2013

The potential utilization of specific attenuation A for rainfall estimation, mitigation of partial beam blockage, and radar networking is investigated. The R(A) relation is less susceptible to the variability of drop size distributions than traditional rainfall algorithms based on radar reflectivity Z, differential reflectivity ZDR, and specific differential phase KDP in a wide range of rain intensity. Specific attenuation is estimated from the radial profile of the measured Z and the total span of the differential phase using the ZPHI method. Since the estimated A is immune to reflectivity biases caused by radar miscalibration, attenuation, partial beam blockage, and wet radomes, rain retrieval from R(A) is also immune to the listed factors. The R(A) method was tested at X band using data collected by closely located radars in Germany and at S band for polarimetrically upgraded Weather Surveillance Radar-1988 Doppler (WSR-88D) radars in the United States.

It is demonstrated that the two adjacent X-band radars—one of which is miscalibrated and another which is affected by partial beam blockage—produce almost indistinguishable fields of rain rate. It is also shown that the R(A) method yields robust estimates of rain rates and rain totals at S band, where specific attenuation is vanishingly small. The X- and S-band estimates of rainfall obtained from R(A) are in good agreement with gauges.
Do children participate in the activities they prefer? A comparison of children and youth with and without physical disabilities
Authors: Bult MK , Verschuren O , Lindeman E , Jongmans MJ , Ketelaar M
Published: October 2013

Objective:

To assess the discrepancy between the leisure activities children prefer and the leisure activities they actually participate in, for children with and without a physical disability, and to explore how in both groups this is related to age and gender.

Design:

Cross-sectional comparison.

Subjects:

Children with and without physical disabilities that were recruited from schools for special education and regular schools in the Netherlands.

Main measures:

The Children’s Assessment of Participation and Enjoyment (CAPE) and the Preferences for Activities of Children (PAC). A discrepancy score was calculated representing high preference but no participation in the activity in the past four months.

Results:

A total of 141 children (6–18 years) with a physical disability (mean age 12.5, 43% girls, 57% boys) and 156 children without physical disabilities (mean age 11.5, 55% girls,45% boys) were included in the study. There was no significant difference in discrepancy scores between children with and without physical disabilities (informal activities 9.8 ± 5.0 vs. 9.8 ± 4.6, formal activities 6.4 ± 3.4 vs. 6.6 ± 2.8). Discrepancy between preference and performance varied by age and gender for children without disabilities but not for children with disabilities.

Conclusions:

Both groups are equally able to participate in the activities they prefer. Age and gender had a significant effect on the discrepancy scores for children and adolescents without physical disabilities but not for children with physical disabilities.
The Influence of Religiosity on Violent Behavior of Adolescents
Authors: Baier Dirk
Published: October 2013

Different criminological theories assume that religiosity protects against violent behavior. Up to now, this assumption is tested empirically almost exclusively for the Christian religiosity. The study presented here questions whether such a relationship between religiosity and violent behavior could be found for Muslims, likewise. Using a German-wide representative school survey of 16,545 male students in the ninth grade, who belong either to a Christian or an Islamic denomination, it can be revealed that only for Christians a higher religiosity correlates with a lower rate of violent behavior. This influence of Christian religiosity can be explained by mainly control theory variables. For Muslims, there is no significant correlation between religiosity and violent behavior in a bivariate analysis. A multivariate analysis, however, reveals a suppression effect: Controlling for alcohol consumption, Muslim religiosity increases violent behavior. In addition, high religious Muslims agree more often to norms of masculinity and consume more often media violence, which are risk factors of violent behavior. Accordingly, it can be concluded that religiosity is not a violence-protecting factor in general; instead, a more differentiated view for separate religious groups is necessary.
Which Relationality? Whose Personhood? The Christian Understanding of the Person, ‘After-Birth Abortion’ and Embryonic Stem Cell Research
Authors: Mühling Markus , Gilland David A.
Published: October 2013

This article argues that the concept of personhood is intrinsically relational and that a relational understanding of created personhood can be derived from divine personhood and understood systematically in relation to itself, the pre-personal world and to other persons. Insofar as this set of three relationships is understood to be dislocated by sinful self-enclosedness in the penultimate reality and standing in contradiction to the ultimate reality retrospectively constituting it, the article suggests that all created personhood at present could be called ‘potential’ personhood. The article then examines the concept of personhood maintained by Alberto Giubilini and Francesca Minerva in their recent paper on ‘after-birth abortion’ in comparison to Johannes Fischer’s discussion of embryonic stem cell research and personhood. In response to both, the article concludes that it is not possible at present for humans to make a concrete external identification of the divine relation that internally constitutes created personhood. As a result, the article proposes adopting a veil of ignorance with reference to the status of embryonic personhood, as it would be worse to deny the status of personhood to an actual person than to attribute personhood to a non-person.
The affective atmospheres of surveillance
Authors: Ellis Darren , Tucker Ian , Harper David
Published: October 2013

The spaces that surveillance produces can be thought of as ambiguous, entailing elements that are ethereal yet material, geographical yet trans-geographical. Contemporary surveillance systems form numerous connections that involve multiple times, spaces, and bodies. Owing to their ubiquity, normalization, and yet clandestine characteristics, they seem to produce an almost unnoticed aspect of everyday life. The impacts, then, of contemporary surveillance systems appear to be particularly experienced on the margins of consciousness. Thus we find that an empirical analysis of this realm of experience is possible but requires one to look for such things as disruption, disfluency, and hesitation in the text of speech acts rather than clear representation. Through empirical analysis of narratives concerning everyday experiences of living with contemporary surveillance systems, this paper focuses on their possible affective impacts. In turn, we find it more fitting to think about the so-called “surveillance society” in terms of producing “atmospheres” rather than “cultures or assemblages,” and “affects” rather than “emotions.”
Effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus: Subgroup analysis of a double-blind randomized controlled trial
Authors: Mok CC , Ying Shirley KY , Ma KM , Wong CK
Published: October 2013

Objectives

The purpose of this study was to identify the effect of raloxifene on disease activity and vascular biomarkers in patients with systemic lupus erythematosus (SLE).

Methods

Subgroup data were analyzed for postmenopausal female SLE patients who participated in a randomized controlled trial of raloxifene on glucocorticoid-induced osteoporosis. Patients who were receiving a stable daily dose of prednisolone (≤10 mg) for ≥6 months were assigned to receive raloxifene (60 mg/day) or placebo on top of calcium and vitamin D. Disease activity was assessed by the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA), SLE disease activity index (SLEDAI) and physicians’ global assessment (PGA) every three months. Lupus flares were assessed by the SELENA flare instrument. Serial serum levels of homocysteine, high-sensitivity C-reactive protein (hsCRP) and soluble thrombomodulin (sTM) were measured.

Results

A total of 62 patients (30 raloxifene, 32 placebo) were studied (age 52.5 ± 6.7 years; SLE duration 9.3 ± 7.6 years; menopause duration 7.2 ± 6.6 years). The SLEDAI at entry was 1.8 ± 2.3 (SLEDAI ≥ 6 in 8%). After 12 months, a significant gain in bone mineral density (BMD) of the lumbar spine (1.6%, p = 0.02), and reduction in bone resorption and formation markers was observed in the raloxifene but not in the placebo treated patients. The SELENA-SLEDAI and PGA scores area under the curve over 12 months were not significantly different between the two groups. There were three episodes of mild/moderate lupus flares (33% musculoskeletal, 33% dermatological) in the raloxifene group, compared to nine episodes of mild/moderate flares (27% musculoskeletal, 45% dermatological) in the placebo group (p = 0.11). The low density lipoprotein (LDL) cholesterol level increased significantly in the placebo but not raloxifene treated patients. No significant changes in homocysteine, hsCRP and sTM levels were observed in either group of patients.

Conclusions

Raloxifene significantly improves lumbar spine BMD in SLE patients but does not cause an increase in lupus activity or flares.
Before the democratic peace: Racial utopianism, empire and the abolition of war
Authors: Bell Duncan
Published: October 2013

During the final quarter of the 20th century, the democratic peace thesis — the idea that democracies do not fight each other — moved to the centre of scholarly debate throughout the Western world. Much of this work traces its origins to the European Enlightenment, focusing especially on Immanuel Kant. Yet this narrative ignores earlier 20th-century debates about the possibilities of global peace, and the role of democracy within them. In this article, I analyse some prominent, but now largely forgotten, strands of political thinking in the United States and Britain during the first half of the 20th century. They form an important part of the genealogy of the democratic peace thesis. I start by delineating four types of argument about peace that were popular in the 19th century: liberal-systemic, radical-liberal, socialist and republican. I then introduce two other modes of argument that circulated at the turn of the 20th century: the ‘democratic war thesis’ (the idea that democracies are war-prone) and the ‘empire peace thesis’ (the argument that only imperial states are capable of assuring perpetual peace). I follow this with a discussion of racial utopianism — the claim that the unification of the Anglo-Saxons could eliminate war, securing peace and justice on earth. This white supremacist vision was a call for the racial pacification of the globe.
The penal voluntary sector in England and Wales: Beyond neoliberalism?
Authors: Tomczak Philippa J
Published: October 2013

In response to policy developments aiming to increase the involvement of penal voluntary organizations in criminal justice, a recent flurry of commentary has provided a marketized understanding of the penal voluntary sector and attempts to privatize it. Although this commentary has contributed significantly to the limited literature on the sector, the centrality of neoliberal policy in analysis is problematic. This article provides a critique of relevant commentary and offers a new exploration of the penal voluntary sector that extends beyond neoliberalism and marketization. A preliminary exploration of an alternative model is made, using political economy to provide a nuanced and politically enabling understanding of the role of voluntary organizations in criminal justice.
Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D
Authors: Tan Kar Wai , Chong Shu Zhen , Wong Fiona H. S. , Evrard Maximilien , Tan Sandra Min-Li , Keeble Jo , Kemeny D. M. , Ng Lai Guan , Abastado Jean-Pierre , Angeli Véronique
Published: October 2013

Lymphangiogenesis is an important physiological response to inflammatory insult, acting to limit inflammation. Macrophages, dendritic cells, and lymphocytes are known to drive lymphangiogenesis. In this study, we show that neutrophils recruited to sites of inflammation can also coordinate lymphangiogenesis. In the absence of B cells, intranodal lymphangiogenesis induced during prolonged inflammation as a consequence of immunization is dependent on the accumulation of neutrophils. When neutrophils are depleted in wild-type mice developing skin inflammation in response to immunization or contact hypersensitization, lymphangiogenesis is decreased and local inflammation is increased. We demonstrate that neutrophils contribute to lymphangiogenesis primarily by modulating vascular endothelial growth factor (VEGF)-A bioavailability and bioactivity and, to a lesser extent, secreting VEGF-D. We further show that neutrophils increased VEGF-A bioavailability and bioactivity via the secretion of matrix metalloproteinases 9 and heparanase. Together, these findings uncover a novel function for neutrophils as organizers of lymphangiogenesis during inflammation.
Cbl ubiquitination of p85 is essential for Epo-induced EpoR endocytosis
Authors: Bulut Gamze B. , Sulahian Rita , Yao Huiyu , Huang Lily Jun-shen
Published: October 2013

Key Points

Epo-induced EpoR internalization is mediated through a novel Cbl/p85/epsin-1 pathway. Mutated EpoR in primary familial and congenital polycythemia patients cannot activate this pathway, exhibiting excessive Epo signaling.
Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and observational data
Authors: Salih Waleed , Schembri Stuart , Chalmers James D.
Published: October 2013

The 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines proposed “minor” criteria to predict intensive care unit (ICU) admission in patients with community-acquired pneumonia. These criteria were based on expert opinion. Consequently, the authors of the guidelines asked investigators to determine whether the score could be simplified by excluding noncontributory variables.

Each IDSA/ATS minor criterion was validated using a random effects meta-analysis of seven studies. Variables present in <5% of cases or that were nonsignificantly associated with mortality/ICU admission were excluded. A simplified score excluding these variables was tested for prediction of mortality and ICU admission in an established database. Prediction was assessed using the area under the receiver operator characteristic curve (AUC).

Leukopenia (<4000 cells·mm−3), thrombocytopenia (<100 000 cells·mm−3) and hypothermia <36°C occurred in <5% of cases. A simplified score excluding these variables was performed similarly for prediction of mortality, AUC 0.77 (95% CI 0.73–0.81)versus0.78 (95% CI 0.74–0.82) (p=0.9) and intensive care unit admission, AUC 0.85 (95% CI 0.82–0.87)versus0.85 (95% CI 0.82–0.88) (p=0.9). Additional predictors suggested by the IDSA/ATS were associated with mortality and ICU admission, but only incorporating acidosis (pH <7.35) altered the AUC (0.82 (95% CI 0.78–0.86) (p=0.6) for mortality and 0.86 (95% CI 0.82–0.88) (p=0.8) for ICU admission). No improvements were statistically significant.

The IDSA/ATS criteria can be simplified by removing three infrequent variables.
The potential impact of routine testing of individuals with HIV indicator diseases in order to prevent late HIV diagnosis
Authors: Scognamiglio Paola , Chiaradia Giacomina , De Carli Gabriella , Giuliani Massimo , Mastroianni Claudio Maria , Aviani Barbacci Stefano , Buonomini Anna Rita , Grisetti Susanna , Sampaolesi Alessandro , Corpolongo Angela , Orchi Nicoletta , Puro Vincenzo , Ippolito Giuseppe , Girardi Enrico ,   for the SENDIH Study Group
Published: October 2013

Background

The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed.

Methods

We studied a large cohort of individuals newly diagnosed with HIV infection in 13 counselling and testing sites in the Lazio Region, Italy (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and tuberculosis. Logistic regression analysis was performed to estimate association of occurrence of at least one indicator disease with late HIV diagnosis.

Results

In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735). Individuals reporting at least one indicator disease before HIV diagnosis (29% of the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5-0.8) compared to those who did not report a previous indicator disease. 52/890 (5.8%) late presenters were probably already infected at the time the indicator disease was diagnosed, a median of 22.6 months before HIV diagnosis.

Conclusions

Our data suggest that testing for HIV following diagnosis of an indicator disease significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5% of late HIV presenters, diagnosis could have been anticipated if they had been tested when an HIV indicator disease was diagnosed.

However, this strategy for enhancing early HIV diagnosis needs to be complemented by client-centred interventions that aim to increase awareness in people who do not perceive themselves as being at risk for HIV.
Prognostic significance and therapeutic potential of the activation of anaplastic lymphoma kinase/protein kinase B/mammalian target of rapamycin signaling pathway in anaplastic large cell lymphoma
Authors: Gao Ju , Yin Minzhi , Zhu Yiping , Gu Ling , Zhang Yanle , Li Qiang , Jia Cangsong , Ma Zhigui
Published: October 2013

Backgroud

Activation of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway has been demonstrated to be involved in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated tumorigenesis in anaplastic large cell lymphoma (ALCL) and correlated with unfavorable outcome in certain types of other cancers. However, the prognostic value of AKT/mTOR activation in ALCL remains to be fully elucidated. In the present study, we aim to address this question from a clinical perspective by comparing the expressions of the AKT/mTOR signaling molecules in ALCL patients and exploring the therapeutic significance of targeting the AKT/mTOR pathway in ALCL.

Methods

A cohort of 103 patients with ALCL was enrolled in the study. Expression of ALK fusion proteins and the AKT/mTOR signaling phosphoproteins was studied by immunohistochemical (IHC) staining. The pathogenic role of ALK fusion proteins and the therapeutic significance of targeting the ATK/mTOR signaling pathway were further investigated in vitro study with an ALK + ALCL cell line and the NPM-ALK transformed BaF3 cells.

Results

ALK expression was detected in 60% of ALCLs, of which 79% exhibited the presence of NPM-ALK, whereas the remaining 21% expressed variant-ALK fusions. Phosphorylation of AKT, mTOR, 4E-binding protein-1 (4E-BP1), and 70 kDa ribosomal protein S6 kinase polypeptide 1 (p70S6K1) was detected in 76%, 80%, 91%, and 93% of ALCL patients, respectively. Both phospho-AKT (p-AKT) and p-mTOR were correlated to ALK expression, and p-mTOR was closely correlated to p-AKT. Both p-4E-BP1 and p-p70S6K1 were correlated to p-mTOR, but were not correlated to the expression of ALK and p-AKT. Clinically, ALK + ALCL occurred more commonly in younger patients, and ALK + ALCL patients had a much better prognosis than ALK-ALCL cases. However, expression of p-AKT, p-mTOR, p-4E-BP1, or p-p70S6K1 did not have an impact on the clinical outcome. Overexpression of NPM-ALK in a nonmalignant murine pro-B lymphoid cell line, BaF3, induced the cells to become cytokine-independent and resistant to glucocorticoids (GCs). Targeting AKT/mTOR inhibited growth and triggered the apoptotic cell death of ALK + ALCL cells and NPM-ALK transformed BaF3 cells, and also reversed GC resistance induced by overexpression of NPM-ALK.

Conclusions

Overexpression of ALK due to chromosomal translocations is seen in the majority of ALCL patients and endows them with a much better prognosis. The AKT/mTOR signaling pathway is highly activated in ALK + ALCL patients and targeting the AKT/mTOR signaling pathway might confer a great therapeutic potential in ALCL.
L (+)-lactic acid production by pellet-form Rhizopus oryzae NRRL 395on biodiesel crude glycerol
Authors: Vodnar Dan C , Dulf Francisc V , Pop Oana L , Socaciu Carmen
Published: October 2013

Background

Given its availability and low price, glycerol derived from biodiesel industry has become an ideal feedstock for the production of fuels and chemicals. A solution to reduce the negative environmental problems and the cost of biodiesel is to use crude glycerol as carbon source for microbial growth media in order to produce valuable organic chemicals. In the present paper, crude glycerol was used as carbon substrate for production of L (+)-lactic acid using pelletized fungus R. oryzae NRRL 395 on batch fermentation. More, the experiments were conducted on media supplemented with inorganic nutrients and lucerne green juice.

Results

Crude and pure glycerols were first used to produce the highest biomass yield of R. oryzae NRRL 395. An enhanced lactic acid production then followed up using fed-batch fermentation with crude glycerol, inorganic nutrients and lucerne green juice. The optimal crude glycerol concentration for cultivating R. oryzae NRRL 395 was 75 g l-1, which resulted in a fungal biomass yield of 0.72 g g-1 in trial without lucerne green juice addition and 0.83 g g-1 in trial with lucerne green juice. The glycerol consumption rate was 1.04 g l-1 h-1 after 48 h in trial with crude glycerol 75 g l-1 while in trial with crude glycerol 10 g l-1 the lowest rate of 0.12 g l-1 h-1 was registered. The highest L (+)-lactic acid yield (3.72 g g-1) was obtained at the crude glycerol concentration of 75 g l-1 and LGJ 25 g l-1, and the concentration of lactic acid was approximately 48 g l-1.

Conclusions

This work introduced sustainable opportunities for L (+)-lactic acid production via R. oryzae NRRL 395 fermentation on biodiesel crude glycerol media. The results showed good fungal growth on crude glycerol at 75 g l-1 concentration with lucerne green juice supplementation of 25 g l-1. Lucerne green juice provided a good source of nutrients for crude glycerol fermentation, without needs for supplementation with inorganic nutrients. Crude glycerol and lucerne green juice ratio influence the L (+)-lactic acid production, increasing the lactate productivity with the concentration of crude glycerol.
The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and promotes migration and invasion in renal cell carcinoma
Authors: Weissinger Daniel , Tagscherer Katrin E , Macher-Göppinger Stephan , Haferkamp Axel , Wagener Nina , Roth Wilfried
Published: October 2013

Background

Overexpression of Decoy Receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor superfamily, is a common event in several types of cancer. In renal cell carcinoma (RCC), DcR3 overexpression is associated with lymph node and distant metastasis as well as a poor prognosis. However, the functional role and regulation of DcR3 expression in RCC is so far unknown.

Methods

Modulation of DcR3 expression by siRNA and ectopic gene expression, respectively, was performed in ACHN and 769-P RCC cell lines. Functional effects of a modulated DcR3 expression were analyzed with regard to migration, invasion, adhesion, clonogenicity, and proliferation. Furthermore, quantitative RT-PCR and immunoblot analyses were performed to evaluate the expression of downstream mediators of DcR3. In further experiments, luciferase assays, quantitative RT-PCR and immunoblot analyses were applied to study the regulation of DcR3 expression in RCC. Additionally, an ex vivo tissue slice culture technique combined with immunohistochemistry was used to study the regulation of DcR3 expression in human RCC specimens.

Results

Here, we show that DcR3 promotes adhesion, migration and invasiveness of RCC cells. The DcR3-dependent increase in cellular invasiveness is accompanied with an up-regulation of integrin alpha 4, matrixmetalloproteinase 7 and urokinase plasminogen activator (uPA). Further, we identified a signaling pathway regulating DcR3 expression in RCC. Using in vitro experiments as well as an ex vivo RCC tissue slice culture model, we demonstrate that expression of DcR3 is regulated in a PI3K/AKT-dependent manner involving the transcription factor nuclear factor of activated T-cells (NFAT).

Conclusions

Taken together, our results identify DcR3 as a key driver of tumor cell dissemination and suggest DcR3 as a promising target for rational therapy of RCC.
Immune response after systematic lymph node dissection in lung cancer surgery: changes of interleukin-6 level in serum, pleural lavage fluid, and lung supernatant in a dog model
Authors: Park Seong Yong , Kim Dae Joon , Aldohayan Abdullah , Ahmed Iftikhar , Husain Sufia , Al Rikabi Ammar , Aldawlatly Abdulazeem , Al Obied Omar , Hajjar Waseem , Al Nassar Sami
Published: October 2013

Background

Systematic nodal dissection (SND) is regarded as a core component of lung cancer surgery. However, there has been a concern on the increased morbidity associated with SND. This study was performed to investigate whether or not SND induces significant immune response.

Methods

Sixteen dogs were divided into two groups; group 1 (n = 8) underwent thoracotomy only, and group 2 (n = 8) underwent SND after thoracotomy. We compared interleukin-6 (IL-6) levels in serum, pleural lavage fluid and lung supernatant at the time of thoracotomy (T0) and at 2 h(T1) after thoracotomy (group 1) or SND (group 2). Severity of inflammation and IL-6 expression in lung tissue were evaluated in a semi-quantitative manner.

Results

The operative results were comparable. IL-6 was not detected in serum in either group. IL-6 in pleural lavage fluid marginally increased from 4.75 ± 3.74 pg/mL at T0 to 19.75 ± 8.67 pg/mL at T1 in group 1 (P= 0.112), and from 7.75 ± 5.35 pg/mL to 17.72 ± 8.58 pg/mL in group 2 (P= 0.068). IL-6 in lung supernatant increased from 0.36 ± 0.14 pg/mL/mg to 1.15 ± 0.17 pg/mL/mg in group 1 (P= 0.003), and from 0.25 ± 0.08 pg/mL/mg to 0.82 ± 0.17 pg/mL/mg in group 2 (P= 0.001). However, the degree of increase in IL-6 in pleural lavage fluid and lung supernatant were not different between two groups (P= 0.421 andP= 0.448). There was no difference in severity of inflammation and IL-6 expression between groups.

Conclusions

SND did not increase IL-6 in pleural lavage fluid and lung supernatant. This result suggests that SND could be routinely performed in lung cancer surgery without increasing the significant inflammatory response.
Does continuous endurance exercise in water elicit a higher release of ANP and BNP and a higher plasma concentration of FFAs in pre-obese and obese men than high intensity intermittent endurance exercise? – Study protocol for a randomized controlled trial
Authors: Karner-Rezek Klaus , Knechtle Beat , Fenzl Matthias , Gredig Joeri , Rosemann Thomas
Published: October 2013

Background

Atrial natriuretic peptides (ANP) and Brain natriuretic peptides (BNP) stimulate fat cell plasma membrane receptors. They are potent lipolytic agents on isolated fat cells from subcutaneous adipose tissue. The physiological effects of continuous endurance exercise on ANP release and plasma free fatty acids (FFA) concentrations have been well described. The enhancement of fat metabolism using high intensity intermittent exercise protocols has been assessed in more recent investigations. The combined effects of endurance exercise and water immersion on ANP and FFA plasma concentration and the magnitude of excess post-exercise oxygen consumption (EPOC) might be further enhanced by choosing the most effective exercise protocol. Exercise modalities may play a significant role in the future prevention and treatment of obesity.

Methods/design

The two testing trials will be performed according to a randomized and cross-over design. Twenty healthy sedentary pre-obese and obese class-1 men will be scrutinized with regard to their metabolic responses to continuous exercise in water and to high intensity endurance exercise in water. Both trials will be matched for energy expenditure. After preliminary testing, the tests will be conducted as repeated measurements. The two different exercise protocols will be compared. The aims of the study are to investigate (1) whether continuous endurance exercise or high intensity intermittent endurance exercise in water elicits both a higher release of ANP and BNP and a higher plasma concentration of glycerol and (2) to determine whether continuous endurance exercise in water or a high intensity intermittent endurance exercise in water would lead to a more pronounced short term (two hours) EPOC effect.

Discussion

If our hypothesis would be confirmed, the most effective exercise protocol based on the combined effects of high intensity endurance exercise and water immersion on ANP and BNP release and glycerol plasma concentrations can be identified. Moreover, the magnitude of the EPOC effect can be augmented. Our study would provide a major contribution for creating optimized exercise modalities in the prevention and treatment of obesity.

Trial registration

Current controlled trials, ISRCTN95488515
Intratumoral genetic heterogeneity in metastatic melanoma is accompanied by variation in malignant behaviors
Authors: Anaka Matthew , Hudson Christopher , Lo Pu-Han , Do Hongdo , Caballero Otavia L , Davis Ian D , Dobrovic Alexander , Cebon Jonathan , Behren Andreas
Published: October 2013

Background

Intratumoral heterogeneity is a major obstacle for the treatment of cancer, as the presence of even minor populations that are insensitive to therapy can lead to disease relapse. Increased clonal diversity has been correlated with a poor prognosis for cancer patients, and we therefore examined genetic, transcriptional, and functional diversity in metastatic melanoma.

Methods

Amplicon sequencing and SNP microarrays were used to profile somatic mutations and DNA copy number changes in multiple regions from metastatic lesions. Clonal genetic and transcriptional heterogeneity was also assessed in single cell clones from early passage cell lines, which were then subjected to clonogenicity and drug sensitivity assays.

Results

MAPK pathway and tumor suppressor mutations were identified in all regions of the melanoma metastases analyzed. In contrast, we identified copy number abnormalities present in only some regions in addition to homogeneously present changes, suggesting ongoing genetic evolution following metastatic spread. Copy number heterogeneity from a tumor was represented in matched cell line clones, which also varied in their clonogenicity and drug sensitivity. Minor clones were identified based on dissimilarity to the parental cell line, and these clones were the most clonogenic and least sensitive to drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for drug-resistant cells resulted in the adoption of a gene expression profile with features of one of the minor clones, supporting the idea that these populations can mediate disease relapse.

Conclusion

Our results support the hypothesis that minor clones might have major consequences for patient outcomes in melanoma.
Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma
Authors: Marley Kevin , Helfand Stuart C , Simpson Jennifer , Mata John E , Tracewell William G , Brownlee Lisa , Bracha Shay , Séguin Bernard
Published: October 2013

Background

Osteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma.

Methods

Two percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin.

Results

Taurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone.

Conclusions

Taurolidine did not substantially exacerbate bone marrow or gastro-intestinal toxicity however, it is possible that taurolidine increased other toxicities of doxorubicin and carboplatin. Administering taurolidine in combination with 30 mg/m2 doxorubicin in dogs is not recommended but taurolidine in combination with carboplatin (300 mg/m2) appears safe.
Clinical predictive value of manual muscle strength testing during critical illness: an observational cohort study
Authors: Connolly Bronwen A , Jones Gareth D , Curtis Alexandra A , Murphy Patrick B , Douiri Abdel , Hopkinson Nicholas S , Polkey Michael I , Moxham John , Hart Nicholas
Published: October 2013

Introduction

Impaired skeletal muscle function has important clinical outcome implications for survivors of critical illness. Previous studies employing volitional manual muscle testing for diagnosing intensive care unit-acquired weakness (ICU-AW) during the early stages of critical illness have only provided limited data on outcome. This study aimed to determine inter-observer agreement and clinical predictive value of the Medical Research Council sum score (MRC-SS) test in critically ill patients.

Methods

Study 1: Inter-observer agreement for ICU-AW between two clinicians in critically ill patients within ICU (n = 20) was compared with simulated presentations (n = 20). Study 2: MRC-SS at awakening in an unselected sequential ICU cohort was used to determine the clinical predictive value (n = 94) for outcomes of ICU and hospital mortality and length of stay.

Results

Although the intra-class correlation coefficient (ICC) for MRC-SS in the ICU was 0.94 (95% CI 0.85–0.98), κ statistic for diagnosis of ICU-AW (MRC-SS <48/60) was only 0.60 (95% CI 0.25–0.95). Agreement for simulated weakness presentations was almost complete (ICC 1.0 (95% CI 0.99–1.0), with a κ statistic of 1.0 (95% CI 1.0–1.0)). There was no association observed between ability to perform the MRC-SS and clinical outcome and no association between ICU-AW and mortality. Although ICU-AW demonstrated limited positive predictive value for ICU (54.2%; 95% CI 39.2–68.6) and hospital (66.7%; 95% CI 51.6–79.6) length of stay, the negative predictive value for ICU length of stay was clinically acceptable (88.2%; 95% CI 63.6–98.5).

Conclusions

These data highlight the limited clinical applicability of volitional muscle strength testing in critically ill patients. Alternative non-volitional strategies are required for assessment and monitoring of muscle function in the early stages of critical illness.
Interactive effects of competition and predator cues on immune responses of leopard frogs at metamorphosis
Authors: Groner Maya L. , Rollins-Smith Louise A. , Reinert Laura K. , Hempel John , Bier Mark E. , Relyea Rick A.
Published: October 2013

Recent hypotheses suggest that immunosuppression, resulting from altered environmental conditions, may contribute to increased incidence of amphibian disease around the world. Antimicrobial peptides (AMPs) in amphibian skin are an important innate immune defense against fungal, viral and bacterial pathogens. Their release is tightly coupled with release of the stress hormone, norepinephrine. During metamorphosis, AMPs may constitute the primary immune response in the skin of some species because acquired immune functions are temporarily suppressed in order to prevent autoimmunity against new adult antigens. Suppression of AMPs during this transitional stage may impact disease rates. We exposed leopard frog tadpoles (Lithobates pipiens) to a factorial combination of competitor and caged-predator environments and measured their development, growth, and production of hydrophobic skin peptides after metamorphosis. In the absence of predator cues, or if the exposure to predator cues was late in ontogeny, competition caused more than a 250% increase in mass-standardized hydrophobic skin peptides. Predator cues caused a decrease in mass-standardized hydrophobic skin peptides when the exposure was late in ontogeny under low competition, but otherwise had no effect. Liquid chromatography mass spectrometry/mass spectrometry of the skin peptides showed that they may include three previously uncharacterized AMPs in the brevinin and temporin families. Both of these peptide families have previously been shown to inhibit harmful microbes including Batrachochytrium dendrobatidis, the fungal pathogen associated with global amphibian declines. Our study shows that amphibians may be able to adjust their skin peptide defenses in response to stressors that are experienced early in ontogeny and that these effects extend through an important life history transition.
Non-stressful temperature effect on oxidative balance and life history traits in adults fish (Oryzias latipes)
Authors: Hemmer-Brepson Claire , Replumaz Leslie , Romestaing Caroline , Voituron Yann , Daufresne Martin
Published: October 2013

Temperature is well known to affect many biological and ecological traits, and especially of ectotherm species. From a physiological point of view, temperature is also positively correlated to metabolism and is often associated with an increase in reactive oxygen species (ROS) production. It has recently been suggested that ROS play a role in lifespan and resources allocation. However, only a few authors have attempted to explore the relationships between temperature, resources allocation and oxidative balance on ectotherms. Here, we propose to measure the effect of temperature on growth, reproductive effort, offspring quantity and quality, hatching and survival rates and the associated proximal costs with the quantification of oxidative balance elements. We reared adult fish (Oryzias latipes) at two non-stressful temperatures (20°C and 30°C) during a relatively long period (4 months, about the entire adult life). The results show a trade-off between reproduction and maintenance because (i) growth did not significantly differ between the 2 thermal groups. As expected (ii) metabolism is higher for warm-acclimated individuals, but (iii) ROS-dependent damages seem to not differ between the two groups, probably due to the higher rate of activation of (iv) the antioxidant enzyme (SOD) for warm-acclimated fish. These higher metabolisms and allocation toward antioxidant defences, are associated with an earlier reproduction and a lower quality of offspring. These interesting results bring new perspectives in terms of prediction of the impact of global warming on biota through the use of ecological theories based on oxidative balance and metabolism.
Competition with Exclusive Contracts and Market-Share Discounts
Authors: Calzolari Giacomo , Denicolò Vincenzo
Published: October 2013

We analyze firms that compete by means of exclusive contracts and market-share discounts (conditional on the seller's share of customers' total purchases). With incomplete information about demand, firms have a unilateral incentive to use these contractual arrangements to better extract buyers' informational rents. However, exclusive contracts intensify competition, thus reducing prices and profits and (in all Pareto undominated equilibria) increasing welfare. Market-share discounts, by contrast, produce a double marginalization effect that leads to higher prices and harms buyers. We discuss the implications of these results for competition policy. (JEL D43, D83, D86, K21, L14, L42)