Notes

Computerized Phylogenetic Evaluation Using Greatest Shared Great time.
This paper demonstrates that unethical conduct by the US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel led to their recommendation of the Linear Non-Threshold (LNT) Model for radiation risk assessment and its subsequent adoption by the US and the world community. The analysis, which is based largely on preserved communications of the US NAS Genetics Panel members, reveals that Panel members and their administrative leadership at the NAS displayed an integrated series of unethical actions designed to ensure, (1) the acceptance of the LNT and (2) funding to radiation geneticist panel members and professional colleagues. These findings are significant because major public policies in open democracies, such as cancer risk assessment and other issues impacted by public fears of radiation or chemical exposures, require ethical foundations. Recognition of these ethical failures of the BEAR I Genetics Panel should require a high level administrative, legislative and scientific reassessment of the scientific foundations of cancer risk assessment, with the likely result necessitating revision of current policies and practices. The BEAR I Genetics Panel, 1956 Science journal publication should immediately be retracted because it contains deliberate misrepresentations of the scientific record that were designed to manipulate scientific and public opinion on radiation risk assessment in a dishonest manner.Tembusu virus (TMUV) causes disease in poultry, especially in ducks, resulting in abnormality in egg production and with high morbidity and mortality, resulting in great loss in duck farming industry in China and Southeast Asia. Previous studies on the pathogenesis of TMUV infection have been mostly conducted in poultry, with a few studies being undertaken in mice. While TMUV does not cause disease in humans, it has been reported that antibodies against TMUV have been found in serum samples from duck farmers, and thus data on TMUV infection in humans is limited, and the pathogenesis is unclear. In this study we investigated the cell tropism and potential susceptibility of humans to TMUV using several human cell lines. The results showed that human nerve and liver cell lines were both highly susceptible and permissive, while human kidney cells were susceptible and permissive, albeit to a lower degree. In addition, human muscle cells, lung epithelial cells, B-cells, T-cells and monocytic cells were largely refractory to TMUV infection. This data suggests that liver, neuron and kidney are potential target organs during TMUV infection in humans, consistent with what has been found in animal studies.
Previous studies have shown that the forkhead transcription factor FoxO6 involved in memory consolidation and hepatic glucose homeostasis. Here we asked whether chicken FoxO6 may regulate preadipocyte proliferation, apoptosis and early adipogenesis.

Overexpression and knockdown of FoxO6 were performed and evaluated through cell proliferation methods, Oil-Red-O staining, and specific marker expression. Chromatin immunoprecipitation (ChIP) assay was performed to confirm cyclin G2 (CCNG2) as a direct target gene of FoxO6.

FoxO6 is ubiquitously expressed in different chicken tissues and highly expressed in liver, abdominal fat, and preadipocytes in cultured cell. FoxO6 overexpression decreased preadipocyte proliferation by causing G1-phase cell-cycle arrest, whereas inhibition of FoxO6 showed the opposite effects. Overexpression or knockdown of FoxO6 significantly altered the mRNA and protein levels of cell-cycle related markers, such as CCNG2, cyclin dependent kinase inhibitor 1B (CDKN1B), cyclin dependent kinase inhibitor 1A (CDKN1A) and cyclin D2 (CCND2). During preadipocyte proliferation, FoxO6 targets and induces expression of CCNG2, as confirmed by ChIP assay and qPCR. In addition, FoxO6 induces preadipocyte apoptosis through increasing the protein expression levels of cleaved caspase-3 and cleaved caspase-8. Moreover, FoxO6 at the early stage of adipogenesis suppressed mRNA and protein levels of the key early regulators of adipogenesis, such as PPARγ and C/EBPα.

The results demonstrate that FoxO6 controls preadipocyte proliferation, apoptosis and early adipogenesis, and point to new approaches for further studies related to obesity.
The results demonstrate that FoxO6 controls preadipocyte proliferation, apoptosis and early adipogenesis, and point to new approaches for further studies related to obesity.The sting of different wasp species triggers local and systemic reactions in victims that can lead to death. Parachartergus fraternus is responsible for frequent accidents in Latin America; however, few studies have been conducted on this insect and its venom. In this study, the inflammatory process induced by the venom of the P. fraternus wasp (Pfv; 100, 200, and 400 μg/kg) was characterized. Mice were used to assess paw edema, vascular permeability, mast cell degranulation, leukocyte influx, nitric oxide (NO) production, expression of inflammatory genes, and histopathological changes. Pfv triggered edema formation with a peak dose of 200 μg/kg at 10 min. There was an increase in permeability in all periods and doses evaluated, with no differences between them. The 200 μg/kg dose induced mast cell degranulation in all periods, with a peak at 15 min. This same dose induced leukocyte influx with a predominance of mononuclear cells and triggered a peak in NO production in the 12th hour. The increase in COX-2, iNOS, and IFN-γ mRNA expression occurred after 1 and 6 h, and there was an increase in IL-10 expression after 48 h. In addition, Pfv triggered edema and induced an influx of macrophages and mast cells into the injection site. Therefore, Pfv induces an inflammatory process from the first 5 min of inoculation that can persist for up to 48 h.
The decision-making on antiplatelet drug withdrawal or continuation before performing a pleural procedure is based on the balance between the risk of bleeding associated with the antiplatelet therapy and the risk of arterial thrombosis due to its interruption. Knowledge on antiplatelet therapy-associated risk of bleeding after pleural procedures is lacking.

Is the risk of bleeding associated with antiplatelet drugs increased in patients undergoing pleural procedures?

We conducted a French multicenter cohort study in 19 centers. The main outcome was the occurrence of bleeding, defined as hematoma, hemoptysis, or hemothorax, during the 24h following a pleural procedure. Serious bleeding events were defined as bleeding requiring blood transfusion, respiratory support, endotracheal intubation, embolization, or surgery, or as death.

A total of 1,124 patients was included (men, 66%; median age, 62.6 ± 27.7 years), of whom 182 were receiving antiplatelet therapy and 942 were not. Fifteen patients experiencedural procedure bleeding and serious bleeding. Future guidelines should take into account these results for patient safety.Porcine hemagglutinating encephalomyelitis virus (PHEV) is a member of the genus Betacoronavirus and is the etiologic agent of encephalomyelitis or vomiting and wasting disease in neonatal pigs. Although there are only a few epidemiological studies that document the seroprevalence of PHEV infection, there are reports of sporadic outbreaks, including recent documentation of an influenza-like respiratory disease associated with PHEV in the United States. To address this issue, we have developed a new indirect enzyme linked immunosorbent assay (ELISA) for use in sero-epidemiological research of PHEV infection. One hundred and fifty porcine serum samples that were determined as antibody-positive or antibody-negative in virus neutralization (VN) tests were used in conjunction with PHEV-specific antigen extracted from virus-infected FS-L3 cells using RBS buffer containing 0.2 % NP-40 to develop this assay. The ELISA showed a high sensitivity (95.35 %) and specificity (96.88 %) by receiver operating characteristic (ROC) analysis, with an area under the curve (AUC) of 0.996 attesting to its accuracy. Our results revealed a strong correlation between the results of the indirect ELISA and VN test (R = 0.850, P less then 0.05), with near-perfect agreement (kappa value = 0.932). These results indicate that this new indirect ELISA might be useful for diagnosis and sero-epidemiological tracking of PHEV infection.Three highly pathogenic human coronaviruses can cause severe acute respiratory syndrome (SARS-CoV, SARS-CoV-2 and MERS-CoV). Although phylogenetic analyses have indicated ancient origin of human coronaviruses from animal relatives, their evolutionary history remains to be established. Using phylogenetics and "high order genomic structures" including trimer spectrums, codon usage and dinucleotide suppression, we observed distinct clustering of all human coronaviruses that formed phylogenetic clades with their closest animal relatives, indicating they have encompassed long evolutionary histories within specific ecological niches before jumping species barrier to infect humans. The close relationships between SARS-CoV and SARS-CoV-2 imply similar evolutionary origin. However, a lower Effective Codon Number (ENC) pattern and CpG dinucleotide suppression in SARS-CoV-2 genomes compared to SARS-CoV and MERS-CoV may imply a better host fitness, and thus their success in sustaining a pandemic. Characterization of coronavirus heterogeneity via complementary approaches enriches our understanding on the evolution and virus-host interaction of these emerging human pathogens while the underlying mechanistic basis in pathogenicity warrants further investigation.The European Union's REACH Regulation requires determination of potential health and environmental effects of chemicals in commerce. The present case study examines the application of REACH guidance for health hazard assessments of three high production volume (HPV) aluminium (Al) substances metallic aluminium, aluminium oxide, and aluminium hydroxide. Among the potential adverse health consequences of aluminium exposure, neurotoxicity is one of the most sensitive targets of Al toxicity and the most critical endpoint. This case study illustrates integration of data from multiple lines of evidence into REACH weight of evidence evaluations. This case study then explains how those results support regulatory decisions on classification and labelling. Challenges in the REACH appraisal of Al compounds include speciation, solubility and bioavailability, application of assessment factors, read-across rationale and differences with existing regulatory standards. Lessons learned from the present case study relate to identification and evaluation of toxicologic and epidemiologic data; assessing data relevance and reliability; development of derived no-effect levels (DNELs); addressing data gaps and preparation of chemical safety reports.Cannabidiol, approved for treatment of pediatric refractory epilepsy, has anti-seizure effects in various animal seizure models. Chemical warfare nerve agents, including soman, are organophosphorus chemicals that can induce seizure and death if untreated or if treatment is delayed. Our objective was to evaluate whether cannabidiol would ameliorate soman-induced toxicity using a mouse model that similar to humans lacks plasma carboxylesterase. In the present study, adult female plasma carboxylesterase knockout (Es1-/-) mice were pre-treated with cannabidiol (20-150 mg/kg) or vehicle 1 h prior to exposure to a seizure-inducing dose of soman and evaluated for survival and seizure activity. The muscarinic antagonist atropine sulfate and the oxime HI-6 were administered at 1 min after exposure, and the benzodiazepine midazolam was administered at 30 min after seizure onset. selleck chemical Cannabidiol (150 mg/kg) pre-treatment led to a robust increase in survival rate and attenuated body weight loss in soman-exposed mice treated with medical countermeasures, compared to mice pre-treated with vehicle.
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