Effect of several calcium sources on cation leaching using soil columns

Soil columns under controlled conditions were used to determine the movement of calcium and other cations after the application of lime, calcium oxide, gypsum and a mixture of Ume and gypsum, compared with a control treatment. Two Oxisols with different textures were used: clayey and silty. Rigid polyvinyl chloride (PVC) columns (length, 45cm; diam, 5cm) were used, applying 1.8 1 of water to each divided into four applications. Exchangeable cations were determined in the drainage water in 4 periods and in 5 dephts of the soil columns at the end of the experiment. The results showed that losses of Ca2+, Mg2+, K+ and A1(3+), were higher in the treatments with gypsum and lime plus gypsum. Amendments h'ke lime and calcium oxide did not promote significant losses of cations. Large losses occured in the silty and clayey soils in the first and second drainage times respectively. Gypsum did not modify the pH of both soils, but reduced cation amounts mainly in the clayey soil. Lime and calcium oxide raised the pH only near the application layer.No estudo realizado em colunas de solo montadas em laboratório, procurou-se avaliar o movimento do cálcio, e de outros cátions, após aplicação de calcário agrícola, gesso, calcário calcinado e uma mistura de calcário agrícola e gesso, comparados com um tratamento testemunha, em dois latossolos vermelho escuros de texturas diferentes: média e argilosa. Utilizaram-se colunas de PVC, com 5cm de diâmetro e 45cm de altura, e aplicaram-se em cada coluna 1,8 litros de água, parcelados em quatro vezes. Determinaram-se os cátions trocáveis presentes na água percolada e, no final do experimento, em cinco profundidades de cada solo. Os resultados mostraram que nos tratamentos gesso e calcário mais gesso as quantidades de Ca2+, Mg2+, K+ e Al3+ na solução percolada foram maiores, enquanto que os tratamentos calcário agrícola e calcário calcinado não promoveram perdas significativas de cátions. As maiores perdas ocorreram na primeira percolação no solo de textura média e na segunda no solo de textura argilosa. O gesso não modificou o pH dos solos, mas reduziu teores de bases no solo argiloso, enquanto que os calcários corrigiram o solo apenas próximo à camada de incorporação

Fanconi anemia and vaginal squamous cell carcinoma

Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis, pulmonary fungal infection, and severe rectal bleeding, followed by hypocalcaemia, hypokalemia, vaginal bacterial and fungal infection, with subsequent leg and arm phlebitis, perineal abscess, and sepsis. The patient died 12 weeks later

Identification of a novel zinc metalloprotease through a global analysis of clostridium difficile extracellular proteins

Clostridium difficile is a major cause of infectious diarrhea worldwide. Although the cell surface proteins are recognized to be important in clostridial pathogenesis, biological functions of only a few are known. Also, apart from the toxins, proteins exported by C. difficile into the extracellular milieu have been poorly studied. In order to identify novel extracellular factors of C. difficile, we analyzed bacterial culture supernatants prepared from clinical isolates, 630 and R20291, using liquid chromatography-tandem mass spectrometry. The majority of the proteins identified were non-canonical extracellular proteins. These could be largely classified into proteins associated to the cell wall (including CWPs and extracellular hydrolases), transporters and flagellar proteins. Seven unknown hypothetical proteins were also identified. One of these proteins, CD630_28300, shared sequence similarity with the anthrax lethal factor, a known zinc metallopeptidase. We demonstrated that CD630_28300 (named Zmp1) binds zinc and is able to cleave fibronectin and fibrinogen in vitro in a zinc-dependent manner. Using site-directed mutagenesis, we identified residues important in zinc binding and enzymatic activity. Furthermore, we demonstrated that Zmp1 destabilizes the fibronectin network produced by human fibroblasts. Thus, by analyzing the exoproteome of C. difficile, we identified a novel extracellular metalloprotease that may be important in key steps of clostridial pathogenesis

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. Methods: Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 x 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively. Results: The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. Conclusion: Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment.30Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Radiology of the Hospital Estadual Sumare UNICAMPSCOGConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNPq [401327/05-1

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al