Distribuição longitudinal de Chironomidae (Diptera) abaixo de uma barragem em um rio neotropical

The damming of a river causes dangerous consequences on structure of the environment downstream of the dam, modifying the sediment composition, which impose major adjustments in longitudinal distribution of benthic community. The construction of Engenheiro Sérgio Motta Dam in the Upper Paraná River has caused impacts on the aquatic communities, which are not yet fully known. This work aimed to provide more information about the effects of this impoundment on the structure of Chironomidae larvae assemblage. The analysis of data of physical and chemical variables in relation to biological data of 8 longitudinal sections in the Upper Paraná River showed that composition of Chironomidae larvae of stations near Engenheiro Sérgio Motta Dam differed of the other stations (farther of the Dam) The predominance of coarse sediments at stations upstream and finer sediments further downstream affected the choice of habitat by different morphotypes of Chironomidae and it caused a change in the structure of this assemblage in the longitudinal stretch.O barramento de um rio pode causar graves consequências sobre a natureza do ambiente, abaixo da barragem, modificando a composição do sedimento, as quais impõem importantes ajustes da distribuição longitudinal das comunidades bentônicas. A construção da Usina Hidrelétrica Engenheiro Sérgio Motta no alto rio Paraná, tem causado impactos em várias comunidades aquáticas, que ainda não são totalmente conhecidos. Este trabalho objetivou fornecer mais informações sobre os efeitos desse represamento na assembleia de Chironomidae. A análise das variáveis físicas e químicas em relação aos dados biológicos de oito transectos longitudinais no alto rio Paraná revelou que a composição das larvas de Chironomidae das estações mais próximas à barragem da Usina Engenheiro Sérgio Motta diferiu das demais (estações mais distantes). A predominância de sedimentos mais grosseiros nas estações a montante e sedimentos mais finos mais a jusante afetou a escolha de habitat pelos diferentes morfotipos de Chironomidae, que levou a alteração na estrutura desta assembleia ao longo do trecho amostrado.Fil: Pinha, G. D.. Universidade Estadual de Maringá. Programa de Pós-Graduação em Ecologia de Ambientes Aquáticos Continentais; Brasil.;Fil: Aviz, D.. Universidade Federal Do Pará; Brasil.;Fil: Lopes Filho, D. R.. Universidade Estadual de Maringá. Programa de Pós-Graduação em Ecologia de Ambientes Aquáticos Continentais; Brasil.;Fil: Petsch, D. K.. Universidade Estadual de Maringá. Programa de Pós-Graduação em Ecologia de Ambientes Aquáticos Continentais; Brasil.;Fil: Marchese Garello, Mercedes Rosa. Consejo Nacional de Investigaciones científicas y Técnicas. Centro Científico Tecnológico CONICET- Santa Fe. Instituto Nacional de Limnologia (i); Argentina;Fil: Takeda, A. M.. Universidade Estadual de Maringá; Brasil.

Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential

Background: Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification. Methods: Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry. Results: Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM. Conclusion: The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets

Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120

For reasons of efficiency Escherichia coli is used today as the microbial factory for production of plasmid DNA vaccines. To avoid hazardous antibiotic resistance genes and endotoxins from plasmid systems used nowadays, we have developed a system based on the food-grade Lactococcus lactis and a plasmid without antibiotic resistance genes. We compared the L. lactis system to a traditional one in E. coli using identical vaccine constructs encoding the gp120 of HIV-1. Transfection studies showed comparable gp120 expression levels using both vector systems. Intramuscular immunization of mice with L. lactis vectors developed comparable gp120 antibody titers as mice receiving E. coli vectors. In contrast, the induction of the cytolytic response was lower using the L. lactis vector. Inclusion of CpG motifs in the plasmids increased T-cell activation more when the E. coli rather than the L. lactis vector was used. This could be due to the different DNA content of the vector backbones. Interestingly, stimulation of splenocytes showed higher adjuvant effect of the L. lactis plasmid. The study suggests the developed L. lactis plasmid system as new alternative DNA vaccine system with improved safety features. The different immune inducing properties using similar gene expression units, but different vector backbones and production hosts give information of the adjuvant role of the silent plasmid backbone. The results also show that correlation between the in vitro adjuvanticity of plasmid DNA and its capacity to induce cellular and humoral immune responses in mice is not straight forward

Polyphosphates as a source of enhanced P fluxes in marine sediments overlain by anoxic waters: Evidence from (31)P NMR

Sedimentary phosphorus (P) composition was investigated in Effingham Inlet, a fjord located on the west coast of Vancouver Island in Barkley Sound. Solid-state (31)P nuclear magnetic resonance (NMR) spectroscopy was applied to demineralized sediment samples from sites overlain by oxic and anoxic bottom waters. The two sites were similar in terms of key diagenetic parameters, including the mass accumulation rate, integrated sulfate reduction rate, and bulk sediment organic carbon content. In contrast, P benthic fluxes were much higher at the anoxic site. (31)P NMR results show that P esters and phosphonates are the major organic P species present at the surface and at depth in sediments at both sites. Polyphosphates were only found in the surface sediment of the site overlain by oxic waters. The varying stability of polyphosphates in microorganisms under different redox conditions may, in part, explain their distribution as well as differences in P flux between the two sites

Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling

The primary biological function of the endogenous cellular prion protein has remained unclear. We investigated its biological function in the generation of cellular immune responses using cellular prion protein gene-specific small interfering ribonucleic acid in vivo and in vitro. Our results were confirmed by blocking cellular prion protein with monovalent antibodies and by using cellular prion protein-deficient and -transgenic mice. In vivo prion protein gene-small interfering ribonucleic acid treatment effects were of limited duration, restricted to secondary lymphoid organs and resulted in a 70% reduction of cellular prion protein expression in leukocytes. Disruption of cellular prion protein signalling augmented antigen-specific activation and proliferation, and enhanced T cell receptor signalling, resulting in zeta-chain-associated protein-70 phosphorylation and nuclear factor of activated T cells/activator protein 1 transcriptional activity. In vivo prion protein gene-small interfering ribonucleic acid treatment promoted T cell differentiation towards pro-inflammatory phenotypes and increased survival of antigen-specific T cells. Cellular prion protein silencing with small interfering ribonucleic acid also resulted in the worsening of actively induced and adoptively transferred experimental autoimmune encephalomyelitis. Finally, treatment of myelin basic protein1–11 T cell receptor transgenic mice with prion protein gene-small interfering ribonucleic acid resulted in spontaneous experimental autoimmune encephalomyelitis. Thus, central nervous system autoimmune disease was modulated at all stages of disease: the generation of the T cell effector response, the elicitation of T effector function and the perpetuation of cellular immune responses. Our findings indicate that cellular prion protein regulates T cell receptor-mediated T cell activation, differentiation and survival. Defects in autoimmunity are restricted to the immune system and not the central nervous system. Our data identify cellular prion protein as a regulator of cellular immunological homoeostasis and suggest cellular prion protein as a novel potential target for therapeutic immunomodulation

Direct application of compound-specific radiocarbon analysis of leaf waxes to establish lacustrine sediment chronology

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Paleolimnology 39 (2008): 43-60, doi:10.1007/s10933-007-9094-1.This study demonstrates use of compound-specific radiocarbon analysis (CSRA) for dating Holocene lacustrine sediments from carbonate-hosted Ordy Pond, Oahu, Hawaii. Long-chain odd-numbered normal alkanes (n-alkanes), biomarkers characteristic of terrestrial higher plants, were ubiquitous in Ordy Pond sediments. The δ13C of individual n-alkanes ranged from −29.9 to −25.5‰, within the expected range for n-alkanes synthesized by land plants using the C3 or C4 carbon fixation pathway. The 14C ages of n-alkanes determined by CSRA showed remarkably good agreement with 14C dates of rare plant macrofossils obtained from nearby sedimentary horizons. In general, CSRA of n-alkanes successfully refined the age-control of the sediments. The sum of n-alkanes in each sample produced 70–170 μg of carbon (C), however, greater age errors were confirmed for samples containing less than 80 μg of C. The 14C age of n-alkanes from one particular sedimentary horizon was 4,155 years older than the value expected from the refined age-control, resulting in an apparent and arguable age discrepancy. Several lines of evidence suggest that this particular sample was contaminated by introduction of 14C-free C during preparative capillary gas chromatography. This study simultaneously highlighted the promising potential of CSRA for paleo-applications and the risks of contamination associated with micro-scale 14C measurement of individual organic compounds.This project was funded by Petroleum Research Fund (PRF #40088-ACS) and in part by Sigma Xi, The Scientific Research Society (Grants in aid of research, 2003)

Optimization of Non-Coding Regions for a Non-Modified mRNA COVID-19 Vaccine

The CVnCoV (CureVac) mRNA vaccine for SARS-CoV-2 has recently been evaluated in a phase 2b/3 efficacy trial in humans1. CV2CoV is a second-generation mRNA vaccine with non-modified nucleosides but optimized non-coding regions and enhanced antigen expression. Here we report a head-to-head study of the immunogenicity and protective efficacy of CVnCoV and CV2CoV in nonhuman primates. We immunized 18 cynomolgus macaques with two doses of 12 ug of lipid nanoparticle formulated CVnCoV, CV2CoV, or sham (N=6/group). CV2CoV induced substantially higher binding and neutralizing antibodies, memory B cell responses, and T cell responses as compared with CVnCoV. CV2CoV also induced more potent neutralizing antibody responses against SARS-CoV-2 variants, including the delta variant. Moreover, CV2CoV proved comparably immunogenic to the BNT162b2 (Pfizer) vaccine in macaques. While CVnCoV provided partial protection against SARS-CoV-2 challenge, CV2CoV afforded more robust protection with markedly lower viral loads in the upper and lower respiratory tract. Binding and neutralizing antibody titers correlated with protective efficacy. These data demonstrate that optimization of non-coding regions can greatly improve the immunogenicity and protective efficacy of a non-modified mRNA SARS-CoV-2 vaccine in nonhuman primates