Cytokine expanded myeloid precursors function as regulatory antigen presenting cells and induce tolerance through IL-10 producing regulatory T cells

The initiation of graft vs. host disease (GVHD) after stem cell transplantation is dependent on direct antigen presentation by host antigen presenting cells (APC) while the effect of indirect antigen presentation by donor APC is unknown. We have studied the role of indirect antigen presentation in allogenic responses by adding populations of cytokine-expanded donor APC to haematopoietic grafts that would otherwise induce lethal GVHD. Progenipoietin-1 (a synthetic G-CSF/Flt-3 L molecule) and G-CSF expanded myeloid DC, plasmacytoid DC and a novel granulocyte-monocyte precursor population (GM) that differentiate into class IIpos, CD80/CD86pos, CD40neg APC during GVHD. Whereas addition of plasmacytoid and myeloid donor DC augmented GVHD, GM cells induced transplant tolerance via MHC class II restricted generation of IL-10-secreting regulatory T cells. Thus a population of cytokine expanded granulocyte-monocyte precursors function as regulatory antigen presenting cells, suggesting that G-CSF derivatives may have application in disorders characterised by a loss of self-tolerance.

The Internationalization Process as Generator Element of Dynamic Capacities: the case of WEG in Argentina and China

The objective of he article is to research the dynamic capacities developed and used by WEG in its internationalization process and to explain how these capacities help the company defends and supports competitive advantage. The article presents an exploratory study of the internationalization process of WEG in Argentina and China. This article has as analysis approach the dynamic capacities, contributes to the literature of international management in two aspects. First, it adds the analytical look of the internationalization based on dynamic capacities that are still well restricted. Second, when working the dynamic capacities as central element of the analysis of the internationalization process, it Proposes one framework of integrative analysis of the economic and behavioral theories that are used to explain the process of companies`-internationalization, although they are dealt independently and sometimes antagonistic way. The result shows as the dynamic capacities are articulated in the base of WEG in its process of internationalization for Argentina and the subsequent movement for China. The developed dynamic capacities in Argentina were acquired for the Brazilian headquarter and could have been applied in the process of internationalization for China. However, a more complex organizational structure cannot be identified where the inter-subsidiary relationships could share dynamic capacities as proposed in framework.

Stakeholders Theory and Theory of the Firm: a study on the hierarchy of objective-functions in Brazilian companies

Discussion opposing the Theory of the Firm to the Theory of Stakeholders are contemporaneous and polemical. One focal point of such debates refers to which objective-function companies, should choose, whether that of the shareholders or that of the stakeholders, and whether it is possible to opt for both simultaneously. Several empirical studies. have attempted-to test a possible correlation between both functions, and there has not been any consensus-so far. The objective of the present research is to examine a gap in such discussions: is there (or not) a subordination of the stakeholders` objective-function to that of the shareholders? The research is empirical,and analytical and employs quantitative methods. Hypotheses were tested and data analyzed by using non-parametrical (chi-square test) and parametrical procedures (frequency. correlation `coefficient). Secondary data was collected from he Economitica database and from the Brazilian Institute of Social and-Economic Analyses (IBASE) website, relative to public companies that have published their Social Balance Statements following the IBASE model from 1999 to 2006, whose sample amounted to 65 companies; In order to assess the objective-function of shareholders a proxy was created based on the following three indices: ROE (return on equity), EnterpriseValue and Tobin`s Q. In order to assess the objective-function of stakeholders a proxy was created by employing the following IBASE social balance indices: internal ones (ISI), external ones (ISE), and environmental ones (IAM). The results have shown no evidence of subordination of stakeholders` objective-function to that of the shareholders in analyzed companies, negating initial expectations and calling for deeper investigation of results. Its main conclusion, which states that the attempted subordination does not take place, is limited to the sample herein investigated and calls for ongoing research aiming at improvements which may lead to sample enlargement and, as a consequence, may make feasible the application of other statistical techniques which may yield a more thorough, analysis of the studied phenomehon.

In the eye of the storm: exploring the introduction of environmental issues in the production function in Brazilian companies

This article aims to analyse the introduction of environmental issues in the context of the production function, which has been referred to as the organisational area to lead corporate environmental management. With that purpose, the theoretical references for corporate environmental management and the necessary alterations in production function have been organised to include environmental aspects, especially in terms of product and process development, quality management, and logistics. Considering that this research field still lacks empirical evidence for Brazilian companies, four case studies were conducted using companies located in the country. The environmental management maturity level of those companies tends to follow the rate with which the environmental issue is introduced in production sub-areas, especially in the product development process. However, in most cases we found that the companies had difficulties in structuring the insertion of the environmental dimension in logistics. The final notes point out the distance observed between what is recommended by international literature and the reality of Brazilian companies in the challenge of making the production function environmentally friendly.

Alterations in cardiac dihydropyridine receptors and calcium channel function in mdx mice

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular condition affecting approximately one in 3500 live male births resulting from the lack of the myocyte protein dystrophin. The absence of dystrophin in cardiac myocytes is associated with calcium overload which in turn activates calcium-dependent proteolytic enzymes contributing to congestive heart failure, muscle necrosis and fibrosis. To date, the basis for the calcium overload has not been determined. Since L-type calcium channels are a major mediator of calcium influx we determined their potential contribution to the calcium overload. Male muscular dystrophy (mdx) mice and control C57BL10ScSn (C57) mice aged 12– 16 weeks were used in all experiments. In tissue bath studies, isolated contracting left atria from mdx revealed a reduced potency to the dihydropyridine (DHP) agonist BayK8644 and antagonist nifedipine (P < 0.05). Similarly, radioligand binding studies using the DHP antagonist [3H]-PN 200-110 showed a reduced potency (P < 0.05) in isolated membranes, associated with an increased receptor density (P < 0.05). The increased receptor density was supported by RT-PCR experiments revealing increased RNAfor the DHP receptor. Patch clamp studies revealed the presence of a diltiazem sensitive calcium current that showed delayed inactivation in isolated mdx myocytes (P < 0.01). In conclusion, the increased number of DHP binding sites and the delay in L-type current inactivation may both contribute to increased calcium influx and hence calcium overload in the dystrophin deficient mdx cardiac myocytes.

Developmental characterization, function and regulation of a Laccase2 encoding gene in the honey bee, Apis mellifera (Hymenoptera, Apinae)

In insects, exoskeleton (cuticle) formation at each molt cycle includes complex biochemical pathways wherein the laccase enzymes (EC 1.10.3.2) may have a key role. We identified an Amlac2 gene that encodes a laccase2 in the honey bee, Apis mellifera, and investigated its function in exoskeleton differentiation. The Amlac2 gene consists of nine exons resulting in an ORE of 2193 nucleotides. The deduced translation product is a 731 amino acid protein of 81.5 kDa and a pl of 6.05. Amlac2 is highly expressed in the integument of pharate adults, and the expression precedes the onset of cuticle pigmentation and the intensification of sclerotization. In accordance with the temporal sequence of exoskeleton differentiation from anterior to posterior direction, the levels of Amlac2 transcript increase earlier in the thoracic than in the abdominal integument. The gene expression lasts even after the bees emerge from brood cells and begin activities in the nest, but declines after the transition to foraging stage, suggesting that maturation of the exoskeleton is completed at this stage. Post-transcriptional knockdown of Amlac2 gene expression resulted in structural abnormalities in the exoskeleton and drastically affected adult eclosion. By setting a ligature between the thorax and abdomen of early pupae we could delay the increase in hemolymph ecdysteroid levels in the abdomen. This severely impaired the increase in Amlac2 transcript levels and also the differentiation of the abdominal exoskeleton. Taken together, these results indicate that Amlac2 expression is controlled by ecdysteroids and has a critical role in the differentiation of the adult exoskeleton of honey bees. (C) 2010 Elsevier Ltd. All rights reserved.

Differential Toxicity of Disperse Red 1 and Disperse Red 13 in the Ames Test, HepG2 Cytotoxicity Assay, and Daphnia Acute Toxicity Test

Azo dyes are of environmental concern due to their degradation products, widespread use, and low-removal rate during conventional treatment. Their toxic properties are related to the nature and position of the substituents with respect to the aromatic rings and amino nitrogen atom. The dyes Disperse Red 1 and Disperse Red 13 were tested for Salmonella mutagenicity, cell viability by annexin V, and propidium iodide in HepG2 and by aquatic toxicity assays using daphnids. Both dyes tested positive in the Salmonella assay, and the suggestion was made that these compounds induce mainly frame-shift mutations and that the enzymes nitroreductase and O-acetyltransferase play an important role in the observed effect. In addition, it was shown that the presence of the chlorine substituent in Disperse Red 13 decreased the mutagenicity about 14 times when compared with Disperse Red 1, which shows the same structure as Disperse Red 13, but without the chlorine substituent. The presence of this substituent did not cause cytotoxicity in HepG2 cells, but toxicity to the water flea Daphnia similis increased in the presence of the chlorine substituent. These data suggest that the insertion of a chlorine substituent could be an alternative in the design of dyes with low-mutagenic potency, although the ecotoxicity should be carefully evaluated. (C) 2010 Wiley Periodicals, Inc. Environ Toxicol 26: 489-497, 2011.

Falls prevention in rural general practice: what stands the test of time and where to from here?

Objective: General practitioner recall of the 1992-96 'Stay on Your Feet'(SOYF) program and its influence on practice were surveyed five years post-intervention to gauge sustainability of the SOYF General Practice (GP) component. Methods: A survey assessed which SOYF components were still in existence, current practice related to falls prevention, and interest in professional development. All general practitioners (GPs) situated within the boundaries of a rural Area Health Service were mailed a survey in late 2001. Results: Response rate was 66.5% (139/ 209). Of 117 GPs in practice at the time of SOYF, 80.2% reported having heard of SOYF and 74.4% of those felt it had influenced practice. Half (50.9%) still had a copy of the SOYF GP resource and of those, 58.6% used it at least 'occasionally'. Three-quarters of GPs surveyed (75.2%) checked medications 'most/almost all' of the time with patients over 60 years; 46.7% assessed falls risk factors; 41.3% gave advice; and 22.6% referred to allied health practitioners. GPs indicated a strong interest in falls prevention- related professional development. There was no significant association between use of the SOYF resource package and any of the current falls prevention practices (all chi(2)>0.05). Conclusions and implications: There was high recall of SOYF and a general belief that it influenced practice. There was little indication that use of the resource had any lasting influence on GPs' practices. In future, careful thought needs to go into designing a program that has potential to affect long-term change in GPs' falls prevention practice.

Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function

Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A individuals, compared with -9% in G/G individuals (p = 0.024). When considering TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.

Effects of reversible inactivation of the medial septum on rat exploratory behavior in the elevated plus-maze using a test-retest paradigm

The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test-retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information. (C) 2010 Elsevier B.V. All rights reserved.