Advances in the field of nanooncology

Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

Mapping and pyramiding of two major genes for resistance to the brown planthopper (Nilaparvata lugens [Stål]) in the rice cultivar ADR52

The brown planthopper (BPH), Nilaparvata lugens (Stål), is one of the most serious and destructive pests of rice, and can be found throughout the rice-growing areas of Asia. To date, more than 24 major BPH-resistance genes have been reported in several Oryza sativa ssp. indica cultivars and wild relatives. Here, we report the genetic basis of the high level of BPH resistance derived from an Indian rice cultivar, ADR52, which was previously identified as resistant to the whitebacked planthopper (Sogatella furcifera [Horváth]). An F2 population derived from a cross between ADR52 and a susceptible cultivar, Taichung 65 (T65), was used for quantitative trait locus (QTL) analysis. Antibiosis testing showed that multiple loci controlled the high level of BPH resistance in this F2 population. Further linkage analysis using backcross populations resulted in the identification of BPH-resistance (antibiosis) gene loci from ADR52. BPH25 co-segregated with marker S00310 on the distal end of the short arm of chromosome 6, and BPH26 co-segregated with marker RM5479 on the long arm of chromosome 12. To characterize the virulence of the most recently migrated BPH strain in Japan, preliminary near-isogenic lines (pre-NILs) and a preliminary pyramided line (pre-PYL) carrying BPH25 and BPH26 were evaluated. Although both pre-NILs were susceptible to the virulent BPH strain, the pre-PYL exhibited a high level of resistance. The pyramiding of resistance genes is therefore likely to be effective for increasing the durability of resistance against the new virulent BPH strain in Japan

Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Phosphorothioated oligonucleotides (PS-ONs) have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs) and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV) infections in vitro and in vivo was therefore investigated.</p> <p>Results</p> <p>In vitro, a 40 mer degenerate AP (REP 9) inhibited both murine CMV (MCMV) and guinea pig CMV (GPCMV) with an IC₅₀of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C) inhibited MCMV with an IC₅₀of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs) was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism <it>in vivo</it>. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers.</p> <p>Conclusion</p> <p>These studies indicate that APs exhibit potent, well tolerated antiviral activity against CMV infection in vivo and represent a new class of broad spectrum anti-herpetic agents.</p

Single Nucleotide Polymorphism in Gene Encoding Transcription Factor Prep1 Is Associated with HIV-1-Associated Dementia

BACKGROUND: Infection with HIV-1 may result in severe cognitive and motor impairment, referred to as HIV-1-associated dementia (HAD). While its prevalence has dropped significantly in the era of combination antiretroviral therapy, milder neurocognitive disorders persist with a high prevalence. To identify additional therapeutic targets for treating HIV-associated neurocognitive disorders, several candidate gene polymorphisms have been evaluated, but few have been replicated across multiple studies. METHODS: We here tested 7 candidate gene polymorphisms for association with HAD in a case-control study consisting of 86 HAD cases and 246 non-HAD AIDS patients as controls. Since infected monocytes and macrophages are thought to play an important role in the infection of the brain, 5 recently identified single nucleotide polymorphisms (SNPs) affecting HIV-1 replication in macrophages in vitro were also tested. RESULTS: The CCR5 wt/Δ32 genotype was only associated with HAD in individuals who developed AIDS prior to 1991, in agreement with the observed fading effect of this genotype on viral load set point. A significant difference in genotype distribution among all cases and controls irrespective of year of AIDS diagnosis was found only for a SNP in candidate gene PREP1 (p = 1.2 × 10(-5)). Prep1 has recently been identified as a transcription factor preferentially binding the -2,518 G allele in the promoter of the gene encoding MCP-1, a protein with a well established role in the etiology of HAD. CONCLUSION: These results support previous findings suggesting an important role for MCP-1 in the onset of HIV-1-associated neurocognitive disorders

T2K neutrino flux prediction

cited By 15 art_number: 012001 affiliation: Centre for Particle Physics, Department of Physics, University of Alberta, Edmonton, AB, Canada; Albert Einstein Center for Fundamental Physics, Laboratory for High Energy Physics (LHEP), University of Bern, Bern, Switzerland; Department of Physics, Boston University, Boston, MA, United States; Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada; Department of Physics and Astronomy, University of California Irvine, Irvine, CA, United States; IRFU, CEA Saclay, Gif-sur-Yvette, France; Institute for Universe and Elementary Particles, Chonnam National University, Gwangju, South Korea; Department of Physics, University of Colorado at Boulder, Boulder, CO, United States; Department of Physics, Colorado State University, Fort Collins, CO, United States; Department of Physics, Dongshin University, Naju, South Korea; Department of Physics, Duke University, Durham, NC, United States; IN2P3-CNRS, Laboratoire Leprince-Ringuet, Ecole Polytechnique, Palaiseau, France; Institute for Particle Physics, ETH Zurich, Zurich, Switzerland; Section de Physique, DPNC, University of Geneva, Geneva, Switzerland; H. Niewodniczanski Institute of Nuclear Physics PAN, Cracow, Poland; High Energy Accelerator Research Organization (KEK), Tsukuba, Ibaraki, Japan; Institut de Fisica d’Altes Energies (IFAE), Bellaterra (Barcelona), Spain; IFIC (CSIC and University of Valencia), Valencia, Spain; Department of Physics, Imperial College London, London, United Kingdom; INFN Sezione di Bari, Dipartimento Interuniversitario di Fisica, Università e Politecnico di Bari, Bari, Italy; INFN Sezione di Napoli and Dipartimento di Fisica, Università di Napoli, Napoli, Italy; INFN Sezione di Padova, Dipartimento di Fisica, Università di Padova, Padova, Italy; INFN Sezione di Roma, Università di Roma la Sapienza, Roma, Italy; Institute for Nuclear Research, Russian Academy of Sciences, Moscow, Russian Federation; Kobe University, Kobe, Japan; Department of Physics, Kyoto University, Kyoto, Japan; Physics Department, Lancaster University, Lancaster, United Kingdom; Department of Physics, University of Liverpool, Liverpool, United Kingdom; Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA, United States; Université de Lyon, Université Claude Bernard Lyon 1, IPN Lyon (IN2P3), Villeurbanne, France; Department of Physics, Miyagi University of Education, Sendai, Japan; National Centre for Nuclear Research, Warsaw, Poland; State University of New York at Stony Brook, Stony Brook, NY, United States; Department of Physics and Astronomy, Osaka City University, Department of Physics, Osaka, Japan; Department of Physics, Oxford University, Oxford, United Kingdom; UPMC, Université Paris Diderot, Laboratoire de Physique Nucléaire et de Hautes Energies (LPNHE), Paris, France; Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA, United States; School of Physics, Queen Mary University of London, London, United Kingdom; Department of Physics, University of Regina, Regina, SK, Canada; Department of Physics and Astronomy, University of Rochester, Rochester, NY, United States; III. Physikalisches Institut, RWTH Aachen University, Aachen, Germany; Department of Physics and Astronomy, Seoul National University, Seoul, South Korea; Department of Physics and Astronomy, University of Sheffield, Sheffield, United Kingdom; University of Silesia, Institute of Physics, Katowice, Poland; STFC, Rutherford Appleton Laboratory, Harwell Oxford, Warrington, United Kingdom; Department of Physics, University of Tokyo, Tokyo, Japan; Institute for Cosmic Ray Research, Kamioka Observatory, University of Tokyo, Kamioka, Japan; Institute for Cosmic Ray Research, Research Center for Cosmic Neutrinos, University of Tokyo, Kashiwa, Japan; Department of Physics, University of Toronto, Toronto, ON, Canada; TRIUMF, Vancouver, BC, Canada; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada; Faculty of Physics, University of Warsaw, Warsaw, Poland; Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland; Department of Physics, University of Warwick, Coventry, United Kingdom; Department of Physics, University of Washington, Seattle, WA, United States; Department of Physics, University of Winnipeg, Winnipeg, MB, Canada; Faculty of Physics and Astronomy, Wroclaw University, Wroclaw, Poland; Department of Physics and Astronomy, York University, Toronto, ON, Canada references: Astier, P., (2003) Nucl. 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Factors associated with stunting among children according to the level of food insecurity in the household: a cross-sectional study in a rural community of Southeastern Kenya

Background: Chronic malnutrition or stunting among children under 5 years old is affected by several household environmental factors, such as food insecurity, disease burden, and poverty. However, not all children experience stunting even in food insecure conditions. To seek a solution at the local level for preventing stunting, a cross-sectional study was conducted in southeastern Kenya, an area with a high level of food insecurity. Methods: The study was based on a cohort organized to monitor the anthropometric status of children. A structured questionnaire collected information on the following: demographic characteristics, household food security based on the Household Food Insecurity Access Scale (HFIAS), household socioeconomic status (SES), and child health status. The associations between stunting and potential predictors were examined by bivariate and multivariate stepwise logistic regression analyses. Furthermore, analyses stratified by level of food security were conducted to specify factors associated with child stunting in different food insecure groups. Results: Among 404 children, the prevalence of stunting was 23.3%. The percentage of households with severe food insecurity was 62.5%. In multivariative analysis, there was no statistically significant association with child stunting. However, further analyses conducted separately according to level of food security showed the following significant associations: in the severely food insecure households, feeding tea/porridge with milk (adjusted Odds Ratio [aOR]: 3.22; 95% Confidence Interval [95% CI]: 1.43-7.25); age 2 to 3 years compared with 0 to 5 months old (aOR: 4.04; 95% CI: 1.01-16.14); in households without severe food insecurity, animal rearing (aOR: 3.24; 95% CI: 1.04-10.07); SES with lowest status as reference (aOR range: from 0.13 to 0.22). The number of siblings younger than school age was not significantly associated, but was marginally associated in the latter household group (aOR: 2.81; 95% CI: 0.92-8.58). Conclusions: Our results suggest that measures against childhood stunting should be optimized according to food security level observed in each community