Deletion of Tumor Necrosis Factor-alpha Receptor 1 (TNFR1) Protects against Diet-induced Obesity by Means of Increased Thermogenesis

In diet-induced obesity, hypothalamic and systemic inflammatory factors trigger intracellular mechanisms that lead to resistance to the main adipostatic hormones, leptin and insulin. Tumor necrosis factor-alpha (TNF-alpha) is one of the main inflammatory factors produced during this process and its mechanistic role as an inducer of leptin and insulin resistance has been widely investigated. Most of TNF-alpha inflammatory signals are delivered by TNF receptor 1 (R1); however, the role played by this receptor in the context of obesity-associated inflammation is not completely known. Here, we show that TNFR1 knock-out (TNFR1 KO) mice are protected from diet-induced obesity due to increased thermogenesis. Under standard rodent chow or a high-fat diet, TNFR1 KO gain significantly less body mass despite increased caloric intake. Visceral adiposity and mean adipocyte diameter are reduced and blood concentrations of insulin and leptin are lower. Protection from hypothalamic leptin resistance is evidenced by increased leptin-induced suppression of food intake and preserved activation of leptin signal transduction through JAK2, STAT3, and FOXO1. Under the high-fat diet, TNFR1 KO mice present a significantly increased expression of the thermogenesis-related neurotransmitter, TRH. Further evidence of increased thermogenesis includes increased O(2) consumption in respirometry measurements, increased expressions of UCP1 and UCP3 in brown adipose tissue and skeletal muscle, respectively, and increased O(2) consumption by isolated skeletal muscle fiber mitochondria. This demonstrates that TNF-alpha signaling through TNFR1 is an important mechanism involved in obesity-associated defective thermogenesis.

Regulation of redox and DNA repair genes by arsenic : low dose protection against oxidative stress?

We have evaluated the molecular responses of human epithelial cells to low dose arsenic to ascertain how target cells may respond to physiologically relevant concentrations of arsenic. Data gathered in numerous experiments in different cell types all point to the same conclusion: low dose arsenic induces what appears to be a protective response against subsequent exposure to oxidative stress or DNA damage, whereas higher doses often provoke synergistic toxicity. In particular, exposure to low, sub-toxic doses of arsenite, As(III), causes coordinate up-regulation of multiple redox and redox-related genes including thioredoxin (Trx) and glutathione reductase (GR). Glutathione peroxidase (GPx) is down-regulated in fibroblasts, but up-regulated in keratinocytes, as is glutathione S-transferase (GST). The maximum effect on these redox genes occurs after 24 h exposure to 5–10 mM As(III). This is 10-fold higher than the maximum As(III) concentrations required for induction of DNA repair genes, but within the dose region where DNA repair genes are co-ordinately down-regulated. These changes in gene regulation are brought about in part by changes in DNA binding activity of the transcription factors activating protein-1 (AP-1), nuclear factor kappa-B, and cAMP response element binding protein (CREB). Although sub-acute exposure to micromolar As(III) up-regulates transcription factor binding, chronic exposure to submicromolar As(III) causes persistent down-regulation of this response. Similar long-term exposure to micromolar concentrations of arsenate in drinking water results in a decrease in skin tumour formation in dimethylbenzanthracene (DMBA)/phorbol 12-tetradecanoate 13-acetate (TPA) treated mice. Altered response patterns after long exposure to As(III) may play a significant role in As(III) toxicology in ways that may not be predicted by experimental protocols using short-term exposures.

Information security, cyber crime, and infrastructure protection : information security management within Australian healthcare organisations

Information security is now recognised as critical factor within the healthcare industry. With the gradual move from paper -based to electronic information there is an even greater need for protection. However, financial and operational constraints often exist which influence the practicality of developing a secure system. A new baseline security standard, the Health Information Security Management Implementation Guide, has been drafted which applies specifically to the unique information security requirements of the healthcare industry. The aim of this paper is to look at the effectiveness of the health information security standard and the development of information security within the Australian healthcare industry.

Can we obtain realistic parameter estimates for the 'protection for sale' model?

In the Grossman and Helpman (1994) model of endogenous trade protection, sectoral lobbies try to influence an incumbent government that maximizes a weighted sum of political contributions and aggregate welfare. We empirically investigate this model using U.S. and Turkish data. Our specification is more tightly tied to theory than those in existing studies. Additionally, we assume all specific‐factor owners to be organized into different lobbies. These changes, validated by hypothesis tests, yield more realistic parameter estimates of the government's concern for aggregate welfare and of the fraction of population organized into lobbies.

Granulocyte colony-stimulating factor receptor: stimulating granulopoiesis and much more

The granulocyte colony-stimulating factor receptor (G-CSFR) plays an important role in the production, survival and activation of neutrophilic granulocytes during both normal and emergency hematopoiesis. The G-CSFR also participates in the development of other myeloid lineages, the mobilization of hematopoietic stem cells and myeloid cell migration. This has lead to several important clinical applications for its ligand, G-CSF. More recently, additional important roles for G-CSFR have emerged outside the hematopoietic system, such as in the protection and repair of a diverse range of tissues, including muscle, liver and neural tissue, providing further scope for developing G-CSF as a therapeutic agent. The G-CSFR has also been implicated in the etiology of disease, with mutations/variants of G-CSFR implicated in neutropenia, myelodysplasia and leukemia. Additionally, autocrine/paracrine stimulation of G-CSFR may be important in the biology of solid tumors, including metastasis.

A generic framework for three-factor authentication : preserving security and privacy in distributed systems

As part of the security within distributed systems, various services and resources need protection from unauthorized use. Remote authentication is the most commonly used method to determine the identity of a remote client. This paper investigates a systematic approach for authenticating clients by three factors, namely password, smart card, and biometrics. A generic and secure framework is proposed to upgrade two-factor authentication to three-factor authentication. The conversion not only significantly improves the information assurance at low cost but also protects client privacy in distributed systems. In addition, our framework retains several practice-friendly properties of the underlying two-factor authentication, which we believe is of independent interest.

Chromate replacement in coatings for corrosion protection of aerospace aluminium alloys

Mixed rare earth organophosphates have been investigated as potential corrosion inhibitors for AA2024-T3 with the aim of replacing chromate-based technologies. Cerium diphenyl phosphate (Ce(dpp) 3) and mischmetal diphenyl phosphate (Mm(dpp) 3) were added to epoxy coatings applied to AA2024-T3 panels and they were effective in reducing the amount and rate of filiform corrosion in high humidity conditions. Ce(dpp) 3 was the most effective and characterisation of the coating formulations showed approximately a factor of 5 reduction in both the number of corrosion filaments initiated as well as the length of these. Mm(dpp) 3 appeared to reduce the corrosion growth rate by a factor of 2 although it was the more effective inhibitor in solution studies. Spectroscopic characterisation of the coatings indicated that the cerium based inhibitor may disrupt network formation in the epoxy thus resulting in a coating that absorbed more water and allowed greater solubilisation of the corrosion inhibiting compound.

Understanding the effects of electrical interference signals and the environment on the effectiveness of cathodic protection

Cathodic protection (CP) failure due to excursions from safe CP levels is a challenge for the protection and maintenance of buried energy pipelines. Although research shows that stray current is a major factor contributing to CP failure, there is little consensus on how 'big' the excursions (either in magnitude, length or frequency) need to be in order to cause pipeline corrosion problems. This uncertainty has caused difficulties in selecting suitable parameters in relevant industry standards. This paper provides a brief review of past research on different factors affecting CP efficiency. Preliminary results from new electrochemical cells designed to develop an understanding of how CP excursions away from the 'safe' level can lead to corrosion problems are also presented.

Sustainable miracles : protection and competition in the Brazilian oil industry

It is often suggested that competition improves productivity, however, the underlying support for this idea is surprisingly thin. This paper presents a case study examining the e ects of a change in the competitive environment on productivity at the Petrobras, Brazil's state-owned oil company. Petrobras had a legal monopoly on production, re ning, transportation and importation of oil in Brazil until it was removed in 1995. Even though Petrobras continues to have a de facto monopoly, the end of legal monopoly labor productivity growth rate more than doubled. A growth accounting of the industry shows that between 1977 and 1993 output growth rate (and productivity growth rate) is explained by the accumulation of capital, while Total Factor Productivity (TFP) decreased. Between 1994 and 2000 labor productivity growth rate is completely explained by the growth rate of TFP. The results suggest that the threat of competition alone is su cient to improve productivity. They also provide evidence that restricting competition help cause Brazil's depression of the 1980s.

Drinking water as a risk factor to poultry health

In the poultry industry, the use of water with adequate physical, chemical and microbiological quality it is of fundamental importance. Since many birds have access to the same water source, quality problems will affect a great number of animals. The drinking water plays an important role in the transmission of some bacterial, viral and protozoan diseases that are among the most common poultry diseases. Important factors to prevent waterborne diseases in broiler production are the protection of supply sources, water disinfection and the quality control of microbiological, chemical and physical characteristics. Water is an essential nutrient for birds and therefore quality preservation is fundamental for good herd performance. The farmer may prevent many diseases in bird flocks by controlling the quality of the ingested water, will certainly result in decreased costs and increased profit, two essential aims of animal production nowadays.

Fault Current Limiter Using YBCO Coated Conductor-The Limiting Factor and Its Recovery Time

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Test of a Modular Fault Current Limiter for 220 V Line Using YBCO Coated Conductor Tapes With Shunt Protection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Leishmania amazonensis TRF ( TTAGGG repeat-binding factor) homologue binds and co-localizes with telomeres

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Proteins of Leishmania (Viannia) shawi confer protection associated with Th1 immune response and memory generation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Factor XIII Val34Leu is a genetic factor involved in the aetiology of venous thrombosis

A mutation in the factor XIII gene (FXIII Val34Leu) gene was recently reported to confer protection against myocardial infarction, but its relationship with venous thrombosis is unknown. In addition, a mutation in the 5'-untranslated region of the FXII gene (46 C→T) was identified which is associated with low plasma levels of the protein. Its prevalence in patients with venous thrombosis is also unknown. We investigated the frequency of the FXIII Val34Leu and FXII 46 C→T mutations in 189 patients with deep venous thrombosis and in 187 age-, gender- and race-matched controls. FXIII Val34Leu was detected in 38.6% of the patients and in 41.2% of the controls. Interestingly, homozygosity for the FXIII mutation was found in 1.6% of the patients and in 9.6% of the controls. yielding an odds ratio (OR) for venous thrombosis of 0.16 (95% CI: 0.05-0.5). The OR for heterozygotes was 1.1 (95% CI: 0.7-1.7). The FXII 46 C→T mutation was detected in 46.0% of the patients and in 48.6% of the controls. The OR for heterozygotes was 0.9 (95% CI: 0.6-1.4) and for homozygotes the OR was 0.8 (95% CI: 0.3-1.9). Our data indicate that the FXII 46 C→T mutation is unlikely to be a major risk factor for venous thrombotic disease. In contrast, the homozygous state for FXIII Val34Leu is a strong protective factor against venous thrombosis, which emerges as a novel generic factor involved in the aetiology of thrombophilia.