STAT3 Activates the Pentraxin 3 Gene in Chronic Lymphocytic Leukemia Cells.

Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells.

STAT3 induces the expression of GLI1 in chronic lymphocytic leukemia cells.

The glioma associated oncogene-1 (GLI1), a downstream effector of the embryonic Hedgehog pathway, was detected in chronic lymphocytic leukemia (CLL), but not normal adult cells. GLI1 activating mutations were identified in 10% of patients with CLL. However, what induces GLI1 expression in GLI1-unmutated CLL cells is unknown.

The costs of mindfulness at work: The moderating role of mindfulness in surface acting, self-control depletion, and performance outcomes.

By and large, research in organizational behavior and psychology has emphasized that mindfulness should have positive implications for employee well-being and performance, largely through benefits to self-control. Although some have noted that mindfulness could also have a "dark side," researchers have yet to examine the potential costs of being mindful at work. Building on prior studies that have found that mindfulness leads to lower levels of surface acting, we investigate the possibility that when mindful employees engage in surface acting, it may contribute to greater self-control depletion, which in turn, results in undesirable performance outcomes.

Synthesis and biological evaluation of a novel photo-activated histone deacetylase inhibitor.

Hydroxamic acid-based histone deacetylase inhibitors (HDACi) are a class of epigenetic agents with potentially broad therapeutic application to several disease states including post angioplasty mediated neointimal hyperplasia (NIH). Precise spatiotemporal control over the release of HDACi at the target blood vessel site is required for the safe and successful therapeutic use of HDACi in the setting of drug eluting balloon catheter (DEBc) angioplasty treatment of NIH. We aimed to develop and characterise a novel photoactive HDACi, as a potential coating agent for DEBc.

No obligation? How gender influences the relationship between perceived organizational support and organizational citizenship behavior.

Previous research indicates that perceived organizational support (POS) elicits felt obligation on the part of employees who, in turn, reciprocate by helping the organization through the performance of organizational citizenship behavior (OCB). However, because gender roles dictate that women should be more helpful than men, women may feel more obligated to engage in OCB even when they experience relatively low levels of POS, whereas men may perform OCB only when they experience relatively high levels of POS. In this article, we use social role theory to predict that the relationship between POS and 3 types of OCB will be stronger for men than for women.

Decreasing formalin concentration improves quality of DNA extracted from formalin-fixed paraffin-embedded tissue specimens without compromising tissue morphology or immunohistochemical staining.

Genomic technologies are increasingly used clinically for both diagnosis and guiding cancer therapy. However, formalin fixation can compromise DNA quality. This study aimed to optimise tissue fixation using normal colon, liver and uterus (n=8 each) by varying neutral buffered formalin (NBF) concentration (1%-5% w/v) and fixation time (24-48 hours).

STAT3-Induced Wnt5a Provides Chronic Lymphocytic Leukemia Cells with Survival Advantage.

The wingless and integration site growth factor-5a (Wnt5a) is a ligand of the receptor tyrosine kinase-like orphan receptor-1 (ROR1). Because both Wnt5a and ROR1 are expressed in circulating chronic lymphocytic leukemia (CLL) cells, and because in other cell types, STAT3, which is constitutively activated in CLL, induces Wnt5a signaling, we wondered whether STAT3 induces the expression of Wnt5a in CLL cells. Sequence analysis detected four putative STAT3 binding sites in close proximity to the Wnt5a gene promoter's start codon.

STAT3 is constitutively acetylated on lysine 685 residues in chronic lymphocytic leukemia cells.

Signal transducer and activator of transcription (STAT)-3 might be phosphorylated or acetylated. Unlike the phosphorylation of STAT3, little is known about the acetylation of STAT3 in chronic lymphocytic leukemia (CLL) cells. Because acetylation activates STAT3 transcription, we sought to study the acetylation status of STAT3 in CLL cells.

STAT3-activated CD36 facilitates fatty acid uptake in chronic lymphocytic leukemia cells.

Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA.

Negative beliefs about accepting coworker help: Implications for employee attitudes, job performance, and reputation.

For more than 30 years, researchers have investigated interpersonal helping in organizations, with much of this work focusing on understanding why employees help their colleagues. Although this is important, it is also critical that employees are willing to accept assistance that is offered by peers. Indeed, helping behavior should only enhance individual and organizational effectiveness if employees are actually willing to accept offers of assistance.

Ibrutinib inhibits free fatty acid metabolism in chronic lymphocytic leukemia.

Unlike normal B-cells, and similar to fat cells, chronic lymphocytic leukemia (CLL) cells aberrantly express lipoprotein lipase (LPL), which contributes to free fatty acids (FFAs) metabolism. Here we show that, in CLL cells, the B-cell receptor (BCR) inhibitor ibrutinib reduced LPL mRNA and protein levels and inhibited FFA metabolism . Likewise, in CLL cells from ibrutinib-treated patients, FFA metabolism was reduced and eventually stopped.

The CXCR4-STAT3-IL-10 Pathway Controls the Immunoregulatory Function of Chronic Lymphocytic Leukemia and Is Modulated by Lenalidomide.

Chronic lymphocytic leukemia (CLL) cells possess regulatory functions comparable to those of normal B10 cells, a regulatory B cell subset that suppresses effector T-cell function through STAT3-mediated IL-10 production. However, the mechanisms governing IL-10 production by CLL cells are not fully understood. Here, we show that the CXC chemokine ligand 12 (CXCL12)-CXCR4-STAT3 axis regulates IL-10 production by CLL cells and their ability to suppress T-cell effector function through an IL-10 mediated mechanism.

Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial.

Background: Disease-related symptoms impair the quality of life of patients with chronic lymphocytic leukaemia (CLL) who do not require systemic therapy. Available therapies are not specifically aimed at symptom control. Because stimulation of the B-cell receptor activates JAK2 in CLL cells and the JAK2 inhibitor ruxolitinib improves symptoms in patients with myelofibrosis, we postulated that ruxolitinib would improve disease-related symptoms in patients with CLL.

Challenges and Successes in the Application of Universal Access Principles in the Development of Bus Rapid Transport Sytems in South Africa.

The National Department of Transport started a programme to upgrade public transport systems throughout South Africa in 2008, which included the upgrading of transport systems for host cities of the 2010 World Cup. This was the first time there was a clear commitment to produce universally accessible public transport systems in South Africa. The requirement to achieve universal access was reinforced by National Treasuries stipulation, that universal access was a precondition for the approval of all funding for these projects.

Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial.

Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks.

High fluorescence in situ hybridization percentage of deletion 11q in patients with chronic lymphocytic leukemia is an independent predictor of adverse outcome.

We have analyzed patients with previously untreated chronic lymphocytic leukemia with del11q fluorescence in situ hybridization (FISH) abnormality (n = 196) in this study. Detection of the 11q22.3 used a multicolor FISH technique.

Probing the penetration of antimicrobial polymyxin lipopeptides into gram-negative bacteria.

The dry antibiotic development pipeline coupled with the emergence of multidrug resistant Gram-negative 'superbugs' has driven the revival of the polymyxin lipopeptide antibiotics. Polymyxin resistance implies a total lack of antibiotics for the treatment of life-threatening infections. The lack of molecular imaging probes that possess native polymyxin-like antibacterial activity is a barrier to understanding the resistance mechanisms and the development of a new generation of polymyxin lipopeptides.

Level of asthma control and health care utilization in Asia-Pacific countries.

Background: Data on the impact of asthma in many countries in the Asia-Pacific region is limited. This study investigated whether partly- and uncontrolled asthma were associated with increased medication use/healthcare utilization and productivity loss among a population of asthma patients from nine Asia-Pacific countries.

Methods: We used cross-sectional data from 3630 asthma patients ≥12 years from the 2011 Asia-Pacific Asthma Insights and Management (AP-AIM) survey.

Thermal pretreatment of algae for anaerobic digestion.

The objective of this work was to determine the benefit of thermal pretreatment on biogas yield from microalgae-fed anaerobic digester mesocosms. Replicate Nanochloropsis oculata cultures were heated for 4h at 30, 60, and 90°C, as well as at a constant temperature of 90°C for 1, 3.5, and 12h.

Avoiding digester upset.

The acetate uptake bioassay (AUB) is a predictive measure for determining the stability of anaerobic digesters, but its use is rare due to the limited availability of gas chromatography equipment at wastewater treatment facilities. A water displacement system was compared and evaluated as an alternative to gas chromatography analysis for conducting the AUB. Results indicated that methane generation rates measured by the two methods were statistically the same.

Molecular determinants of the substrate specificity of the complement-initiating protease, C1r.

The serine protease, C1r, initiates activation of the classical pathway of complement, which is a crucial innate defense mechanism against pathogens and altered-self cells. C1r both autoactivates and subsequently cleaves and activates C1s. Because complement is implicated in many inflammatory diseases, an understanding of the interaction between C1r and its target substrates is required for the design of effective inhibitors of complement activation.

FluCAN 2009: initial results from sentinel surveillance for adult influenza and pneumonia in eight Australian hospitals.

Objective: To describe the epidemiology of adult patients hospitalised with influenza or pneumonia during a pandemic season in a sentinel network in Australia.

Design, Participants And Setting: Prospective case series of adult hospital admissions to eight acute care general public hospitals (Influenza Complications Alert Network [Flu CAN] sentinel hospitals) in six Australian jurisdictions, 1 July to 4 December 2009.

Main Outcome Measures: Demographic, clinical and outcome measures in patients admitted with laboratory-confirmed pandemic (H1N1) 2009 influenza in the sentinel hospitals compared with data from national notifications and intensive care unit (ICU) surveillance; admissions for influenza and pneumonia over time in each jurisdiction.

The effects of pulmonary rehabilitation in patients with non-cystic fibrosis bronchiectasis: protocol for a randomised controlled trial.

Background: Non-cystic fibrosis bronchiectasis is characterised by sputum production, exercise limitation and recurrent infections. Although pulmonary rehabilitation is advocated for this patient group, its effects are unclear. The aims of this study are to determine the short and long term effects of pulmonary rehabilitation on exercise capacity, cough, quality of life and the incidence of acute pulmonary exacerbations.

Effect of mycorrhizal fungi on the phytoremediation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX).

The objective of this research was to decrease the bioaccumulation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) in the leaves of switchgrass (Panicum virgatum) and hybrid poplar trees (Populus deltoides x nigra, DN34) by exploiting the symbiotic relationship between these plants and mycorrhizal fungi. Prior to dosing with uniformly labeled (14)C-RDX, plants were grown for three months to establish the symbiosis. Results showed that the presence of mycorrhizal fungi does not significantly decrease the concentration of RDX in leaf tissues for experimental periods of 30 days.