Photoinduced Photosensitizer-Antibody Conjugates Kill HIV Env-Expressing Cells, Also Inactivating HIV.

HIV-infected cells persist for decades in patients administered with antiretroviral therapy (ART). Meanwhile, an alarming surge in drug-resistant HIV viruses has been occurring. Addressing these issues, we propose the application of photoimmunotherapy (PIT) against not only HIV Env-expressing cells but also HIV. Previously, we showed that a human anti-gp41 antibody (7B2) conjugated to cationic or anionic photosensitizers (PSs) could specifically target and kill the HIV Env-expressing cells. Here, our photolysis studies revealed that the binding of photoimmunoconjugates (PICs) on the membrane of HIV Env-expressing cells is sufficient to induce necrotic cell death due to physical damage to the membrane by singlet oxygen, which is independent of the type of PSs. This finding persuaded us to study the virus photoinactivation of PICs using two HIV-1 strains, X4 HIV-1 NL4-3 and JR-CSF virus. We observed that the PICs could destroy the viral strains, probably via physical damage on the HIV envelope. In conclusion, we report the application of PIT as a possible dual-tool for HIV immunotherapy and ART by killing HIV-expressing cells and cell-free HIV, respectively

Improved estimation of inbreeding and kinship in pigs using optimized SNP panels

BACKGROUND: Traditional breeding programs consider an average pairwise kinship between sibs. Based on pedigree information, the relationship matrix is used for genetic evaluations disregarding variation due to Mendelian sampling. Therefore, inbreeding and kinship coefficients are either over or underestimated resulting in reduction of accuracy of genetic evaluations and genetic progress. Single nucleotide polymorphism (SNPs) can be used to estimate pairwise kinship and individual inbreeding more accurately. The aim of this study was to optimize the selection of markers and determine the required number of SNPs for estimation of kinship and inbreeding. RESULTS: A total of 1,565 animals from three commercial pig populations were analyzed for 28,740 SNPs from the PorcineSNP60 Beadchip. Mean genomic inbreeding was higher than pedigree-based estimates in lines 2 and 3, but lower in line 1. As expected, a larger variation of genomic kinship estimates was observed for half and full sibs than for pedigree-based kinship reflecting Mendelian sampling. Genomic kinship between father-offspring pairs was lower (0.23) than the estimate based on pedigree (0.26). Bootstrap analyses using six reduced SNP panels (n = 500, 1000, 1500, 2000, 2500 and 3000) showed that 2,000 SNPs were able to reproduce the results very close to those obtained using the full set of unlinked markers (n = 7,984-10,235) with high correlations (inbreeding r > 0.82 and kinship r > 0.96) and low variation between different sets with the same number of SNPs. CONCLUSIONS: Variation of kinship between sibs due to Mendelian sampling is better captured using genomic information than the pedigree-based method. Therefore, the reduced sets of SNPs could generate more accurate kinship coefficients between sibs than the pedigree-based method. Variation of genomic kinship of father-offspring pairs is recommended as a parameter to determine accuracy of the method rather than correlation with pedigree-based estimates. Inbreeding and kinship coefficients can be estimated with high accuracy using ≥2,000 unlinked SNPs within all three commercial pig lines evaluated. However, a larger number of SNPs might be necessary in other populations or across lines

Genome wide scan for quantitative trait loci affecting tick resistance in cattle (Bos taurus × Bos indicus)

<p><b>Abstract</b></p> <p><b>Background</b></p> <p>In tropical countries, losses caused by bovine tick <it>Rhipicephalus (Boophilus) microplus</it> infestation have a tremendous economic impact on cattle production systems. Genetic variation between <it>Bos taurus</it> and <it>Bos indicus</it> to tick resistance and molecular biology tools might allow for the identification of molecular markers linked to resistance traits that could be used as an auxiliary tool in selection programs. The objective of this work was to identify QTL associated with tick resistance/susceptibility in a bovine F2 population derived from the Gyr (<it>Bos indicus</it>) × Holstein (<it>Bos taurus</it>) cross.</p> <p>Results</p> <p>Through a whole genome scan with microsatellite markers, we were able to map six genomic regions associated with bovine tick resistance. For most QTL, we have found that depending on the tick evaluation season (dry and rainy) different sets of genes could be involved in the resistance mechanism. We identified dry season specific QTL on BTA 2 and 10, rainy season specific QTL on BTA 5, 11 and 27. We also found a highly significant genome wide QTL for both dry and rainy seasons in the central region of BTA 23.</p> <p>Conclusions</p> <p>The experimental F2 population derived from Gyr × Holstein cross successfully allowed the identification of six highly significant QTL associated with tick resistance in cattle. QTL located on BTA 23 might be related with the bovine histocompatibility complex. Further investigation of these QTL will help to isolate candidate genes involved with tick resistance in cattle.</p

SOD2 immunoexpression predicts lymph node metastasis in penile cancer

BACKGROUND: Superoxide dismutase-2 (SOD2) is considered one of the most important antioxidant enzymes that regulate cellular redox state in normal and tumorigenic cells. Overexpression of this enzyme in lung, gastric, colorectal, breast cancer and cervical cancer malignant tumors has been observed. Its relationship with inguinal lymph node metastasis in penile cancer is unknown. METHODS: SOD2 protein expression levels were determined by immunohistochemistry in 125 usual type squamous cell carcinomas of the penis from a Brazilian cancer center. The casuistic has been characterized by means of descriptive statistics. An exploratory logistic regression has been proposed to evaluate the independent predictive factors of lymph node metastasis. RESULTS: SOD2 expression in more than 50% of cells was observed in 44.8% of primary penile carcinomas of the usual type. This expression pattern was associated with lymph node metastasis both in the uni and multivariate analysis. CONCLUSIONS: Our results indicate that SOD2 expression predicts regional lymph node metastasis. The potential clinical implication of this observation warrants further studies.Dr. Lara Termini (FAPESP 2005/57274-9); Dr. Luisa Lina Villa (FAPESP 2008/57889-1 and CNPq 573799/2008-3)

Impact of amendments on the physical properties of soil under tropical long-term no till conditions

Tropical regions have been considered the world's primary agricultural frontier; however, some physico-chemical deficiencies, such as low soil organic matter content, poor soil structure, high erodibility, soil acidity, and aluminum toxicity, have affected their productive capacity. Lime and gypsum are commonly used to improve soil chemical fertility, but no information exists about the long-term effects of these products on the physical attributes and C protection mechanisms of highly weathered Oxisols. A field trial was conducted in a sandy clay loam (kaolinitic, thermic Typic Haplorthox) under a no-tillage system for 12 years. The trial consisted of four treatments: a control with no soil amendment application, the application of 2.1 Mg ha-1 phosphogypsum, the application of 2.0 Mg ha-1 lime, and the application of lime + phosphogypsum (2.0 + 2.1 Mg ha-1, respectively). Since the experiment was established in 2002, the rates have been applied three times (2002, 2004, and 2010). Surface liming effectively increased water-stable aggregates > 2.0 mm at a depth of up to 0.2 m; however, the association with phosphogypsum was considered a good strategy to improve the macroaggregate stability in subsoil layers (0.20 to 0.40 m). Consequently, both soil amendments applied together increased the mean weight diameter (MWD) and geometric mean diameter (GMD) in all soil layers, with increases of up to 118 and 89%, respectively, according to the soil layer. The formation and stabilization of larger aggregates contributed to a higher accumulation of total organic carbon (TOC) on these structures. In addition to TOC, the MWD and aggregate stability index were positively correlated with Ca2+ and Mg2+ levels and base saturation. Consequently, the increase observed in the aggregate size class resulted in a better organization of soil particles, increasing the macroporosity and reducing the soil bulk density and penetration resistance. Therefore, adequate soil chemical management plays a fundamental role in improving the soil's physical attributes in tropical areas under conservative management and highly affected by compaction caused by intensive farming