Extension of indoor residual spraying for malaria control into high transmission settings in Africa

Contrary to previous consensus, a recent WHO statement recommends a more dominant role for indoor residual spraying (IRS) in malaria control in high transmission settings of sub-Saharan Africa and re-emphasises the role of DDT. We review the issues related to this change in recommendation. In high transmission settings, IRS must be implemented indefinitely and at high quality to achieve control. As current infrastructure limitations and unpredictable funding make this unlikely, each country must carefully consider the role of IRS. There remains a need to support ongoing insecticide-treated net scale-up. Insecticide choice is hampered by the lack of economic costing data.     

The barley stem rust-resistance gene Rpg1 is a novel disease-resistance gene with homology to receptor kinases

Stem rust caused by Puccinia graminis f. sp. tritici was among the most devastating diseases of barley in the northern Great Plains of the U.S. and Canada before the deployment of the stem rust-resistance gene Rpg1 in 1942. Since then, Rpg1 has provided durable protection against stem rust losses in widely grown barley cultivars (cvs.). Extensive efforts to clone Rpg1 by synteny with rice provided excellent flanking markers but failed to yield the gene because it does not seem to exist in rice. Here we report the map-based cloning and characterization of Rpg1. A high-resolution genetic map constructed with 8,518 gametes and a 330-kb bacterial artificial chromosome contig physical map positioned the gene between two crossovers approximately 0.21 centimorgan and 110 kb apart. The region including Rpg1 was searched for potential candidate genes by sequencing low-copy probes. Two receptor kinase-like genes were identified. The candidate gene alleles were sequenced from resistant and susceptible cvs. Only one of the candidate genes showed a pattern of apparently functional gene structure in the resistant cvs. and defective gene structure in the susceptible cvs. identifying it as the Rpg1 gene. Rpg1 encodes a receptor kinase-like protein with two tandem protein kinase domains, a novel structure for a plant disease-resistance gene. Thus, it may represent a new class of plant resistance genes.     

IL‐17 and IL‐22 in immunity: Driving protection and pathology

IL‐17 and IL‐22 are tissue‐signaling cytokines that favor protection and regeneration of barrier organs such as the skin, lung, and gastrointestinal system. Both cytokines share cellular sources, signaling pathways, and functional aspects; however, taking a closer look they differ, e.g. in their pro‐inflammatory or regenerative potential. An imbalance of the carefully orchestrated tissue‐signaling system might result in autoimmune diseases, promote cancer growth, or predispose to infectious diseases. This review highlights recent understandings in cellular sources, signaling mechanisms, physiologic as well as pathogenic role of the double‐faceted cytokines IL‐17 and IL‐22.     

Cytomegalovirus vector expressing RAE‐1γ induces enhanced anti‐tumor capacity of murine CD8+ T cells

Designing CD8⁺ T‐cell vaccines, which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show the robust potential of cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE‐1γ as CD8⁺ T cell‐based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE‐1γ, delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD‐1. CMV vector expressing RAE‐1γ potentiated expansion of KLRG1⁺ CD8⁺ T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long‐term maintenance of epitope‐specific CD8⁺ T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8⁺ T‐cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8⁺ T‐cell sensitive tumors.     

Predictive value of comorbidity and anemia on outcome in patients with sinonasal carcinoma

Introduction

To evaluate the influence of comorbidities and anemia on outcome and survival in patients with sinonasal carcinomas.

Metabolic MR imaging of regional triglyceride and creatine content in the human heart

An optimized echo‐planar spectroscopic imaging sequence is proposed to facilitate spatial mapping of triglyceride and total creatine content in the human heart. The sequence integrates local‐look field of view reduction, cardiac and respiratory gating, and dedicated reconstruction steps to account for gradient channel delays, field inhomogeneity, and phase incoherence due to residual motion. The technique is demonstrated in 12 volunteers in comparison to single voxel point‐resolved spectroscopy in the septal wall at 1.5 T. Triglyceride‐to‐water and total creatine‐to‐water ratios derived from echo‐planar spectroscopic imaging (0.48 ± 0.18% and 0.06 ± 0.03%) and point‐resolved spectroscopy (0.52 ± 0.17% and 0.07 ± 0.02%) were found to agree well. In the septal region, intraclass correlation coefficients ranging from 0.67 to 0.72 were estimated. A relatively weak agreement (intraclass correlation coefficients: 0.34 and 0.52) was found for sectors in the lateral wall due to field gradients induced by the posterior vein and limited sensitivity of the receive coil array in this area. On the basis of the findings, it is concluded that fast spectroscopic imaging of both cardiac triglyceride and total creatine content is feasible. Shimming and sensitivity challenges in the lateral region remain, however, to be addressed. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.     

Effects of the antioxidative vitamins A, C and E on liver metastasis and intrametastatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters.

BACKGROUND/AIMS: Antioxidative vitamins are known to inhibit metastasis. Therefore we evaluated the impact of vitamins A (retinol), C (ascorbic acid) and E (alpha-tocopherol) on liver metastasis in a model of ductal pancreatic adenocarcinoma in hamster. METHODS: One hundred and twenty male Syrian hamsters were randomized into 8 groups (Gr.) (n = 15). Gr. 1-4 were given 0.5 ml normal saline subcutaneously (s.c.) weekly, whereas Gr. 5-8 received 10 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body weight s.c. for 3 months for tumor induction. In the 13th week Gr. 2 and 6 were administered retinol, Gr. 3 and 7 received ascorbic acid and Gr. 4 and 8 were given alpha-tocopherol orally. No treatment was performed in Gr. 1 and 5. After 24 weeks animals were sacrificed, pancreas and liver were histologically determined. Activities of glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD) and concentration of thiobarbituric-acid-reactive substances (TBARS) were analyzed in hepatic tissue. RESULTS: Retinol and alpha-tocopherol decreased the incidence of liver metastases (44.4 vs. 86.7%, p < 0.05). The number and size of liver metastases were significantly reduced by retinol. Activities of GSH-Px and SOD were increased and concentration of TBARS was decreased in NML and LiMe by all vitamins. CONCLUSION: Obviously, antioxidative vitamins prevent oxidative stress in hepatocytes. This may be one mechanism decreasing liver metastasis in pancreatic cancer in the present trial.     

Increased levels of interleukin-1 in bronchoalveolar washings from children with bacterial pulmonary infections

To investigate its role in pulmonary infections, concentrations of interleukin-1 were measured in 22 bronchoalveolar lavage fluid (BALF) samples from 19 children with cystic fibrosis (CF), and in 13 disease controls by enzyme-linked immunosorbent assay (ELISA) for IL-1 beta and the D10.G4.1 proliferation assay for IL-1 activity. Significantly higher levels of IL-1 beta and IL-1 activity were found in BALF from patients with bacterial pulmonary infections than in those without such infection. There was no significant difference between the levels in patients with CF and pulmonary infections and those in children with bacterial infections complicating other diseases. High performance liquid chromatography showed that most of the IL-1 beta was associated with a molecular weight peak of 17 to 18 kD. Pulmonary inflammation reflected by the number of polymorphonuclear leukocytes (PMN) in the sample correlated significantly with the IL-1 concentration.