BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection

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THE PREPARATION AND PROPERTIES OF HIGHLY PURIFIED ASCORBIC ACID OXIDASE

1. A method is described for the preparation of a highly purified ascorbic acid oxidase containing 0.24 per cent copper. 2. Using comparable activity measurements, this oxidase is about one and a half times as active on a dry weight basis as the hitherto most highly purified preparation described by Lovett-Janison and Nelson. The latter contained 0.15 per cent copper. 3. The oxidase activity is proportional to the copper content and the proportionality factor is the same as that reported by Lovett-Janison and Nelson. 4. When dialyzed free of salt, the blue concentrated oxidase solutions precipitate a dark green-blue protein which carries the activity. This may be prevented by keeping the concentrated solutions about 0.1 M in Na₂HPO₄. 5. When highly diluted for activity measurements the oxidase rapidly loses activity (irreversibly) previous to the measurement, unless the dilution is made with a dilute inert protein (gelatin) solution. Therefore activity values obtained using such gelatin-stabilized dilute solutions of the oxidase run considerably higher than values obtained by the Lovett-Janison and Nelson technique. 6. The effect of pH and substrate concentration on the activity of the purified oxidase in the presence and absence of inert protein was studied.     

Comparative Inactivation of Adenovirus Serotypes by UV Light Disinfection

The results of this study confirm that adenoviruses are the most resistant enteric viruses to inactivation by UV light and that adenovirus 40 appears to be the most resistant. The effect of freeze-thawing and storage in water may affect the sensitivity of some adenoviruses to inactivation by UV light.     

Current Status for High Titre Poxvirus Stock Preparation in CEF Under Serum-Free Medium Conditions: Implication for Vaccine Development

In light of the recent detection of BSE in North America and its endemic nature in other regions of the world, there is a real need to employ cell culture conditions that do not require any animal-derived material. Here we report the use of an ultra-low protein serum-free medium (VP-SFM, Invitrogen) for the amplification of poxviruses in primary chicken embryo fibroblasts (CEF). We compared the amplification of four different poxviruses (canarypox, modified Ankara Virus (MVA), vaccinia virus strain Copenhagen and myxoma strain Lausanne) in three different media: DMEM 10%, DMEM 2% and serum-free medium VP-SFM. VP-SFM is a serum-free, ultra-low protein medium containing no proteins or peptides of human or animal origin designed to support the replication of viruses and the production of recombinant proteins and monoclonal antibodies. Our results show that high titre poxvirus stocks can be prepared in VP-SFM equivalent to that prepared in serum containing medium.     

Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model.

Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL-3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals (n = 800) were randomized to be treated with either HRL-3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. Animals received antibiotics and were observed for 168 h. Route but not dose of E. coli altered the effects HRL-3 on mortality rate (mean hazards ratio +/- SE). With IV E. coli, compared with control, HRL-3 was beneficial and reduced the hazards ratio both early (0 to 6 h; -0.75 +/- 0.23) and late (6 to 168 h; -0.72 +/- 0.36) (P = 0.001 and 0.04, respectively, over all E. coli doses). In contrast, with IB E. coli HRL-3 reduced the hazards ratio early (-1.1 +/- 0.36) but worsened it late (0.87 +/- 0.23) (P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli (P < 0.0001). Compared with control, although HRL-3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli (P = ns for all), it reduced both early and increased them late with IB E. coli (P 相似文献   

Potential impacts of climate change on the distributions of several common and rare freshwater fishes in Canada

Climate change will ultimately affect the supply and quality of freshwater lakes and rivers throughout the world. This study examines the potential impacts of climate change on freshwater fish distributions in Canada. Climate normals data (means from 1961 to 1990) from Environment Canada were used to map current climate found throughout the tertiary watersheds of Canada. Logistic regressions based on these climate data were used to develop predictive presence‐absence equations for (a) common commercially and recreationally important species and (b) an Arctic freshwater species and a freshwater fish species of conservation significance listed by the Committee on the Status of Endangered Wildlife (COSEWIC). The Canadian Centre for Climate Modelling and Analysis Global Coupled Model 2(IS92a) provided forecasts of Canada's climate in 2020 and 2050. The data from this scenario and the logistic regressions provided a ready framework for predicting the potential distributions of the fishes. Physical and ecological barriers would have to be overcome for the distribution of these species to actually change in response to climate change. Generally, coldwater species may be extirpated from much of their present range while cool and warm‐water species may expand northward. Species that are limited to the most southern regions of the country may expand northwards. A conceptual framework for assessing potential climate change impacts on fishes and the variety of management strategies required to deal with these impacts are discussed. Our forecasts demonstrate the need for climate change assessments in species at risk as well as for common species.     

Analysis of single nucleotide polymorphisms in the promoter region of interleukin-10 by denaturing high-performance liquid chromatography.

Interleukin-10 (IL10), an anti-inflammatory cytokine, has been implicated in a variety of immune- and inflammatory-related diseases. We investigated the following SNPs: -1082, -819, -592 in the promoter region of IL10 in a normal (control) population and selected diseases: breast cancer (BrCa), systemic lupus erythematosus (SLE), and B-cell chronic lymphocytic leukemia (B-CLL) by denaturing high-performance liquid chromatography (DHPLC) and found distinct genotype and haplotype patterns. DHPLC was performed using the Transgenomic WAVE instrument, a mutational discovery tool that allows for high throughout analysis of SNPs. The principle of DHPLC is based on separation of homo- and heteroduplex formation of individual polymerase chain reaction products at specific melting temperatures and set gradients. The melting temperature selected for each SNP was based on size and sequence of the polymerase chain reaction product (for -1082, 57 degrees C; for -819, 58 degrees C; and for -592, 59.2 degrees C). Before fragment mutational analysis, all samples were denatured at 95 degrees C and slowly reannealed to allow for reassociation of different strands. Heteroduplex samples were easily distinguished from homoduplex samples. In order to identify wild type from homozygous mutant, two homoduplex polymerase chain reaction samples had to be mixed together, denatured at 95 degrees C and reannealed. The homozygous mutant, when combined with wild type, displayed a double peak on chromatogram. Once distinct chromatograms were established for each of the SNPs and the nucleotide changes confirmed by sequencing, genotype and haplotype frequencies were tabulated for the groups studied.